EP1301155A2 - Procedes et appareils destines a ameliorer la chirurgie ophtalmique refractive - Google Patents

Procedes et appareils destines a ameliorer la chirurgie ophtalmique refractive

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Publication number
EP1301155A2
EP1301155A2 EP01954818A EP01954818A EP1301155A2 EP 1301155 A2 EP1301155 A2 EP 1301155A2 EP 01954818 A EP01954818 A EP 01954818A EP 01954818 A EP01954818 A EP 01954818A EP 1301155 A2 EP1301155 A2 EP 1301155A2
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EP
European Patent Office
Prior art keywords
data
operative
post
ablation
comea
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EP01954818A
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German (de)
English (en)
Inventor
Cynthia Roberts
William J. Dupps, Jr.
Noriko Katsube
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Ohio State University
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Ohio State University
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Priority to EP05013025A priority Critical patent/EP1666009A3/fr
Publication of EP1301155A2 publication Critical patent/EP1301155A2/fr
Withdrawn legal-status Critical Current

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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
    • 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
    • A61F9/00802—Methods or devices for eye surgery using laser for photoablation
    • A61F9/00804—Refractive treatments
    • A61F9/00806—Correction of higher orders
    • 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
    • A61F2009/00855—Calibration of the laser system
    • A61F2009/00857—Calibration of the laser system considering biodynamics
    • 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
    • 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
    • A61F2009/00878—Planning
    • A61F2009/00882—Planning based on topography

Definitions

  • the invention relates generally to the field of vision correction and more particularly to methods and apparatus involving biodynamics iomechanics of the eye to ultimately provide improved vision to patients through refractive correction.
  • Ablation and surgical outcome are ultimately linked on two levels: a deterministic, cause-effect relationship dictated by physical reality, and a statistical relationship, rooted in probability and defined in retrospective regression analyses of the same variables in large-scale clinical trials.
  • the ability to objectively measure performance of the eye, as opposed to simple corneal shape, is critical to "customizing" ablation algorithms and generating an overall improvement of visual outcomes after refractive surgery.
  • Anterior corneal surface topography cannot take into account contributions of optically important structures inside the eye, such as the posterior corneal surface and the crystalline lens. If a laser were programmed strictly with anterior topography data, the correction would be at best incomplete, and at worst simply wrong.
  • wavefront analysis is clearly important, particularly if the ultimate goal is to correct higher order aberrations along with the sphere and cylinder.
  • the question must be asked whether wavefront analysis alone is sufficient to fully predict visual outcomes. Will it replace corneal topography in the quest for the perfect "aberration-free"guided procedure? Or, on the other hand, is there a piece of the puzzle still missing? If so, can corneal topography complement the wavefront data to help complete the picture of corneal response?
  • the cornea is a piece of plastic to be sculpted into the "ideal" surface shape.
  • the pre-operative cornea is modeled as a sphere of greater curvature than the desired post-operative cornea, which is also modeled as a sphere.
  • the apex of the desired post-operative cornea is displaced from the pre- operative cornea by the maximal ablation depth, which is determined by the ablation zone size.
  • the intervening tissue is simply removed or "subtracted” to produce the final result. This is illustrated in Figure 2 for a myopic, as well as a hyperopic profile which is similar in concept, but with a different planned ablation profile that produces increased post-operative curvature.
  • shape-subtraction This concept will be referred to as the "shape-subtraction" model of refractive surgery and treats the cornea as if it were a homogeneous structure, like a piece of plastic.
  • the incomplete shape-subtraction paradigm permeates current thinking in refractive surgery, and forms the basis for both topography-guided and wavefront-guided procedures.
  • LASIK laser in-situ keratomileusis
  • the ablation algorithm is the most astonishingly controllable. Consequently, it is often the sole focus of refractive control in developing sophisticated corneal ablation routines based on topographic and/or wavefront analysis.
  • the model of corneal response that contributed to unpredictability in noncustomized procedures still influences the refractive outcome and overall visual performance.
  • empirically modified ablation algorithms have produced reasonable results in many patients, they are unlikely to provide the individual predictability that physicians desire and patients increasingly demand.
  • algorithms derived from these probabilistic models were optimized for the mean population response rather than that of the individual, and a certain degree of prediction error is inescapable.
  • the cornea has been modeled as a biomechanical structure for refractive procedures that do not rely on excimer laser ablation, such as radial keratotomy.
  • excimer laser ablation such as radial keratotomy.
  • the cornea is assumed to be a solid material and the effect of the surgically-induced structural change on corneal deformation, produced by an incisional or other procedure, is investigated.
  • the only mechanical loading condition used in these simulations is the intraocular pressure applied to the posterior surface of the cornea.
  • Living human cornea is highly porous and filled with a biological fluid. In fact, 80 % by weight is considered to be water.
  • the corneal endothelium serves as a biological "fluid-pump", maintaining a state of relative dehydration with a negative intra-stromal pressure (approximately 50 -60 mmHg below the atmospheric pressure) called the "imbibition pressure".
  • the microstructure of the corneal stroma consists of approximately 300 ⁇ 500 lamellar layers throughout its thickness. Each layer consists of collagen fibers supported by a mstrix consisting of "proteoglycans" and water. When living human cornea is incised or ablated, the long collagen fibers are severed in a series of layers.
  • biomechanical response as used herein, the term “biomechanical response,” sometimes used interchangeably with .
  • biodynamic response means a mechanical or physical response to a perturbation or other stimulus - has not been directly incorporated into current ablation algorithms.
  • material properties of living human corneas based on age, sex, race, climate, years of contact lens wear, etc.
  • the ability to predict the biomechanical response of the cornea to a photoablative procedure, and account for it in ablation algorithm design would significant enhance quality of vision produced.
  • the invention pertains most generally to improving visual quality through refractive surgery.
  • An aspect of this general goal is to obtain the highest level of subjective satisfaction of visual quality as measured objectively.
  • the gist of the invention resides in the predictive capability of the biodynamics of the eye.
  • a wide variety of photoablative procedures can benefit from this predictive ability, in a number of ways.
  • LASLK or PRK treatments can be improved by taking pre-operative measurements and predicting the corneas' s biodynamic response to the ablative treatment.
  • predictive use is made of the biodynamic response of the cornea due to laser or mechanical keratectomy, that is, creating a corneal flap characteristic of LASIK.
  • Comparison of pre-flap and post-flap, (pre-ablation) data of the cornea can provide predictive information applicable to modifying an ablation algorithm before the laser is engaged, either for a current operation or the development of a model.
  • Modeling by finite element analysis or other mathematical techniques, can also be used to predict post-operative outcomes based on a pre-operative (no flap cut or other surgical intervention) data for the cornea that is input for an accurate eye model that, in consideration of biodynamic response via the model, provides predictive information for optimizing the success of the refractive surgery and ultimately patient satisfaction.
  • LASIK, PRK and other photoablative techniques benefit from these embodiments of the invention.
  • an embodiment of the invention is directed to a method for performing refractive corneal surgery.
  • the steps include obtaining a pre- operative (e.g.., pre-flap cut for LASIK) diagnostic measurement data of the eye, determining ablation specifications based upon the pre-operative diagnostic measurement data, perturbing the cornea of the eye such that there is a biodynamical response, obtaining a post-pertubation diagnostic measurement of the eye, determining an adjusted ablation specification based at least in part on a comparison of the pre-operative and post-pertubation data wherein these data are indicative of a biodynamical response of the eye, and ablating a portion of the cornea using the adjusted ablation specification.
  • a pre- operative e.g., pre-flap cut for LASIK
  • the post-pertubation measurement may indicate a greater or lesser degree of central corneal flattening and greater or lesser degree of peripheral corneal steepening and thickening.
  • These structural and physiological changes are manifestations of the magmtude of the biodynamic response of the cornea to the pertubation.
  • the magnitude of the biodynamic response can then be used to adjust the ablation specifications, e.g., less central pulses and more peripheral pulses.
  • Another embodiment is directed to a method for establishing a photoablative specification by obtaining a pre-operative (e.g.
  • pre-flap cut diagnostic measurement data of the cornea determining ablation specifications based upon the pre-operative diagnostic measurement data, perturbing the cornea of the eye such that there is a biodynamic response, obtaining a post-pertubation diagnostic measurement of the cornea, and determining an adjusted ablation specification based at least in part on a comparison of the pre-operative and post-pertubation data wherein these data are indicative of a biodynamical response of the eye.
  • a method for correcting and, preferably, optimizing existing algorithms for photoablative ophthalmic surgery that includes taking data of a statistically significant number of corneas.
  • Biomechanical response has not been directly factored into current ablation algorithms.
  • advance measurements of individual characteristics that are related to biodynamic response can be used to predict surgical outcomes.
  • the cornea was treated as a solid material.
  • the highly porous nature of and the normal negative pressure within the cornea is taken into consideration.
  • the central portion of corneal s rface after surgery is shown to flatten.
  • the inventive method which includes the position-dependent negative "imbibition” pressure, the basic chnically known results of LASIK or PRK can be correctly modeled.
  • the clinically observed peripheral thickening after the LASIK or PRK is also demonstrated through the usage of simplified models.
  • the cornea is basically modeled as a fluid-filled porous material as opposed to a solid material in the existing simulations. Therefore, the mechanical loading inside the cornea such as the negative ("imbibition") pressure applied on the internal pore boundary is directly incorporated into the simulations. Because of this major difference between the two methods, the inventive methodologies can reproduce and predict actual clinical physical phenomenon.
  • Figure 1 is a schematic of the simple "shape-substraction" paradigm for correction of myopia.
  • Figure 2 is a schematic diagram of shape-subtraction model of refractive surgery for myopic ablation (left) and hyperopic ablation (right).
  • Figure 3 presents post-operative minus pre-operative difference maps: elevation (upper left), pachymetric (lower left), tangential curvature (upper right) and axial (lower right).
  • Figure 4 is a tangential curvature difference map (post-op minus pre-op) after a LASIK procedure.
  • Figure 5 is a pachymetry difference map (post-op minus pre-op) after a myopic LASIK procedure.
  • Figure 6 has post-op minus pre-op difference maps from a LASIK correction.
  • Figure 7 has error maps of actual minus predicted post-op topography for the same subject as Figure 6.
  • Figures 8 and 9 present maps of: A) pre-operative elevation (left) and tangential curvature (right); B) post-operative elevation (left) and tangential curvature (right); and C) elevation error (left) and tangential curvature error (right).
  • Figure 10 presents regression analysis of peripheral stromal thickness of the superior region (upper plot) and inferior region (lower plot) against curvature.
  • Figure 11 is a conceptual model that predicts biomechanical central flattening as a direct consequence of severed corneal lamellae.
  • Figure 12 is a schematic diagram of the forces described by A) the interlamellar cohesive strength and B) the interlamellar shear strength.
  • Figure 13 illustrates the impact of biomechanics on LASIK nomograms for primary and secondary hyperopia.
  • Figure 14 shows a sample ablation depth profile calculated at 6 months after PRK.
  • Figure 15 is a comparison between planned ablation profiles and measured topographic elevation difference maps.
  • Figure 16 has average difference maps between repeated measures of 20 eyes of 10 normal subjects.
  • Figure 17 has average difference maps between 1 day post-op LASIK and pre-op state.
  • Figure 18 has average difference maps between 1 month post-op LASIK and pre-op state.
  • Figure 19 presents composite difference maps of peripheral increases in curvature (upper right), elevation (upper left), and thickness (lower left) for patients who underwent LASIK surgery and had Orbscan corneal topography pre-operatively and at 6 months post- operatively.
  • Figure 20 presents optical image views of the central region (A) and the inferior (B) superior (C) regions of the cornea.
  • Figure 21 graphs central curvature shifts vs. regional peripheral stromal thickness changes.
  • Figure 22 shows a pre-operative (upper left) and (lower left) curvature topography taken while the patient is supine for a LASIK procedure.
  • Figure 23 the curvature difference map between pre-op and post-flap for the patient in Figure 22, calculated and displayed using customized software.
  • Figure 24 is a model for an intact cornea, presented as a portion of an axisymmetric layered spherical shell fixed at the ends.
  • Figure 25 is a model for cut cornea after PRK or LASIK surgery.
  • Figure 26 illustrates flattening of the model cornea after surgery based on the fhiid- filled porous material assumption of cornea.
  • Figure 27 illustrates bulging of the model cornea after surgery based on the solid material assumption of cornea
  • Figure 28 and 29 compare the overall corneal deformed shapes for intact and cut corneal models, with two different assumptions. Detailed Description
  • Our comprehensive, integrated model of corneal response to laser refractive surgery takes into account three proposed components to the final corneal shape which determines vision: 1) ablation profile and laser parameters; 2) epithelial and stromal healing; and 3) biomechanical response to a change in structure.
  • the third component, biomechanical response has not been directly incorporated into existing ablation profiles in excimer laser refractive procedures. Therefore, this three pronged, systematic model, fully characterizing the corneal response represents an innovative approach to solving this complex problem.
  • an optimization approach is used to develop new ablation algorithms. Using optimization routines to produce the best possible outcome also represents a highly innovative approach to laser refractive surgery. This model and this optimization approach provide answers to the three assumptions or questions discussed above.
  • Assumption #1 can be invalidated by anyone with access to a set of post-operative topography from PRK or LASIK. Outside the ablation zone, curvature significantly increases with the appearance of the characteristic red ring (high dioptric value) surrounding the central flattened zone after a myopic procedure. (Shown in the tangential map, not the axial.) In addition, elevation and pachymetry also increase outside the ablation zone, as measured by Orbscan topography, and shown with an example in Figure 3.
  • Figure 4 is a tangential curvature difference map (post-op minus pre-op) after a -12.5 diopter LASIK procedure using a Technolas 217 (Munich, Germany) with a 5.5mm diameter ablation zone.
  • the topography was acquired using an ORBSCAN I (Salt Lake City, Utah). The data were exported using the recorder function, and subsequently imported into custom software for analysis. Centrally, there is a decrease in curvature, as expected, indicated by the negative values and blue colors.
  • the surrounding thin white area represents zero difference between the pre and post-op state, hi the area outside the ablation zone, there is an unexpected increase in curvature which extends into the periphery, indicated by the positive values and red colors. Changes in corneal curvature clearly occur well beyond the ablation zone, challenging assumption #1.
  • Figure 5 is a pachymetry difference map from the same patient. Inside the ablation zone, the thickness has decreased, as expected. However, outside the ablation zone, the thickness has unexpectedly increased. In addition, regression analysis between the central and peripheral curvature changes showed a significant negative correlation (p ⁇ 0.0053), indicating that greater central flattening produced greater peripheral steepening.
  • peripheral increase in curvature is a known consequence of laser refractive surgery, but has never been fully explained other than as a "knee" at the edge of the ablation profile. If this were an accurate description, the change would be confined near the edge of the ablation zone, and yet it extends well beyond that region. Additional data in the form of elevation and pachymetry maps, from the same patient population, also showed significant peripheral increases in both elevation and pachymetry outside the ablation zone, corresponding to the increase in curvature. These paradoxical changes in elevation and pachymetry have been anecdotally attributed to measurement device errors, without exploration of the responsible biomechanical mechanisms.
  • Figure 6 shows four difference maps from a sample patient in this population with a 6mm ablation zone, including elevation, tangential, axial, and pachymetry differences.
  • the expected decreases in curvature, elevation and pachymetry centrally, within the ablation zone, are noted.
  • the maps also show unexpected increases in elevation, pachymetry, and curvature outside the ablation zone. Therefore, the results of this study challenge the validity of the assumption that corneal curvature changes are confined to the ablation zone.
  • the proposed mechanism for the paradoxical changes in elevation and pachymetry are the subject of this invention.
  • the sample error map in Figure 7 shows a pattern of positive error peripherally in elevation, pachymetry, and curvature with negative error centrally in elevation, pachymetry and somewhat in curvature, although curvature is not consistently negative over the whole central region.
  • These patterns of error cannot simply be attributed to using an estimated rather than known ablation profile, since they are both nonrandom and nonlinear.
  • the actual ablation algorithms should be used in a study of this type, rather than Munnerlyn's formulas, but they were not available due to their proprietary nature.
  • the red area in the center of the tangential curvature error maps correspond to the central island treatment. This treatment involves delivery of extra pulses in the center of the cornea, which would cause excessive flattening IF they were not compensating for the central island phenomenon - the genesis of which is not yet understood. Therefore, the curvature error maps appears to have a "central island” even though the post-operative topographies are smooth.
  • the red areas outside the ablation zone on the tangential curvature error maps correspond to the unexpected increases in curvature, which are not predicted by the shape-subtraction model, and are predicted via the biomechanical model presented herein.
  • the following case study further illustrates how central curvature changes can actually track peripheral thickness changes after ablation.
  • the patient had 6mm diameter PRK (VISX Star) for a refractive error of -3.75 + 0.75 x 90, with Orbscan I topography pre and post-operatively.
  • Both superior and inferior corneal thicknesses were calculated by averaging a 1mm diameter region in the pachymetry map along the vertical meridian, at the edges of a 7.5mm diameter circle centered on the ablation zone.
  • Central curvature was calculated by averaging the curvature in the 3mm diameter central region of the tangential map. The values as a function of time relative to surgery are given in Table 2.
  • Thickness Thickness Curvature (microns) (microns) (microns) preop 715 682 605 41.55 diopters
  • FIGURE 11 A conceptual model is presented in FIGURE 11 that predicts biomechanical central flattening as a direct consequence of severed corneal lamellae.
  • the cornea may be conceived as a series of stacked rubber bands (lamellae) with sponges between each layer (interlamellar spaces filled with ground substance or matrix).
  • the rubber bands are in tension, since there is a force pushing on them from underneath (intraocular pressure), and the ends are held tightly by the limbus.
  • the amount of water that each sponge can hold is determined by how tautly the rubber bands are pulled. The more they are pulled, the greater the tension each carries, the more water is squeezed out of the interleaving sponges, and the smaller the interlamellar spacing.
  • a flap is cut with a microkeratome to a thickness of approximately 160 microns.
  • Biomechanically this is very close to a 160 micron depth ablation, and according to the proposed model, should induce corneal flattening.
  • the amount of flattening produced should be indicative of the biomechanical response of the cornea to refractive surgery.
  • Topography of this epithelial surface of the cornea, before and just after cutting the flap, permits alteration of ablation algorithms in real time to account for individual biomechanics, and improves surgical outcomes.
  • the basis for the proposed biomechanical theory of corneal response lies in the lamellar structure of the corneal stoma, which is altered in PTK, PRK, and LASIK. It is known the stroma dominates the mechanical response of the cornea to injury.
  • the stromal lamellae by virtue of their extension across the corneal width and continuity with the corneo- scleral limbus, bear a tensile load arising from intraocular pressure and extraocular muscle tension.
  • the propensity of the stroma to imbibe fluid and swell which is attributed to the hydrophilic macromolecules of the extracellular matrix, is resisted by the corneal limiting layers, the metabolic activity of the corneal endothelium, and the compressive effects of lamellar tension.
  • the thickness of the stroma is lineraly related to the hydration and thus is an accessible indicator of changes in corneal mechanical equilibrium. It is proposed that when tension-bearing lamellae are disrupted by central keratectomy, their peripheral segments relax, causing local decompression of the extracellular matrix, and a compensatory influx of stromal fluid adding to increases in interlamellar spacing and peripheral thickness.
  • interlamellar crosslinks which are preferentially distributed in the anterior one-third and periphery of the stroma, as depicted schematically in Figure 11, and are postulated to contribute to regional differences in lamellar shearing strength and interlamellar cohesive strength.
  • a pivotal aspect of the model is the prospect that interlamellar stress generated in the expanding stromal periphery is communicated through this lattice of crosslinks to lamellae comprising the postoperative optical surface.
  • Arrows in Figure 11 indicate expansion of the peripheral stromal matrix secondary to ablation-induced lamellar relaxation. Peripheral thickening is proposed to exert an anterolateral tension at the ablation margin and stimulate central flattening.
  • Coupling of peripheral and central tensile loads is mediated by interlamellar cohesive forces ("x") preferentially distributed in the anterior-peripheral stroma (shaded). Components of force in the direction of peripheral expansion result in central corneal flattening and peripheral steepening.
  • x interlamellar cohesive forces
  • PTK and LASIK central ablation causes an immediate circumferential severing of corneal lamellae under tension, with a subsequent relaxation of the corresponding peripheral lamellar segments. This causes a peripheral decompression of the extracellular matrix and an increase in stromal thickness outside of the ablation zone.
  • biomechanical changes in the cornea may produce an acute postoperative flattening of the central cornea and a refractive shift toward hyperopia.
  • This response is perhaps most clearly demonstrated by the clinical phenomenon of unintended hyperopic shift in PTK, but its contribution to refractive variability in PRK and LASIK is also important, since biomechanical central flattening will enhance a procedure to treat myopia and oppose a procedure to treat hyperopia.
  • An additional feature of the model an acute depth-dependent response — will also be discussed.
  • the epithelium Of the five anatomic layers of the cornea, (the epithelium, Bowman's layer, the stroma, Descemet's layer and the endothehum), only Bowman's zone and the stroma contain collagen fibrils. These layers are thus presumed to provide the majority of the corneas' tensile strength.
  • tension in the superficial epithelial cells has been cited as a potential mechanism for maintaining a smooth optical surface in the presence of underlying stromal surface undulations, removal of the epithelium causes little or no change in the anterior corneal curvature, and the epithelium is generally attributed a minimal role in corneal tensile strength.
  • Descemet's layer The mechanics of Descemet's layer ⁇ the 7-um-thick hypertrophied basil lamina of the underlying endothehum — were studied in intact human and rabbit globes, and compared to findings in stroma from the same species. Stress-strain investigations revealed that in the in situ human cornea, the stromal stress-strain curve is quite steep, corresponding to a high Young's modulus, while Descemet's layer is highly extensible. Superimposing the stress- strain curves for the two layers demonstrated that Descemet's layer is essentially unstrained over a large range of intraocular pressures for which the stroma is simultaneously fully strained.
  • Bowman's zone is little more than an acellular extension of the anterior stroma. Relative to the stroma, the individual collagen fibrils are two-thirds smaller (20 to 25 nm in diameter) and more randomly oriented throughout the 8 to 12-um-thick sheet. However, it has long been believed that Bowman's zone contributes a structural rigidity to the cornea that is distinct from that provided by the stroma. But recent studies, using a linear extensiometer to examine a number of mechanical parameters in deepithelialized corneal strips obtained from fresh human cadaver eyes have indicated that removal of Bowman's layer did not significantly alter the constitutive mechanical properties of the cornea.
  • the stroma which makes up about 90% of the total corneal thickness, is the layer thought to most significantly influence the mechanical response of the cornea to injury.
  • the stroma is approximately 78% water by weight, 15% collagen, and 7% other proteins, proteoglycans, and salts.
  • Three hundred to five hundred lamellae flattened bundles of parallel collagen fibrils — run from limbus to limbus without interruption, h the posterior two-thirds of the stroma, the lamellae are successively stacked parallel to the corneal surface such that each lamellae has an angular offset from its anterior and posterior neighbors.
  • the lamellae are more randomly oriented, often obliquely to the corneal surface, are more branched, and are significantly interwoven. These regional differences correlate well with observations that shearing of the lamellae is generally difficult in the human stroma, but particularly so anteriorly. Collagen interweaving is also more extensive in the corneal periphery than in its center.
  • Cohesive strength has been measured as the force required to separate a stromal sample along a cleavage plane parallel to the lamellar axes by pulling in a direction perpendicular to the cleavage plane, like peeling a banana (as shown in Figure 12A).
  • the cohesive strength is a measure of the interlamellar resistance to separation in the transverse direction and is expressed as a function of distance from the corneal center.
  • the shear strength manifests as a resistance to shearing or sliding of one lamellae over another in the plane parallel to the lamellar axes (the longitudinal direction); as such, it is an integrated function of the connective forces across the entire lamellar interface and is therefore conceivably larger in magmtude (Figure 12B). Both forces are likely to contribute to the peripheral-to-central transfer of stress in the proposed biomechanical model of corneal response to laser ablation.
  • the interlamellar cohesive strengths of the temporal and nasal peripheries of the horizontal meridian were equivalent in the study referred to above, cursory studies of the vertical meridian revealed large and consistent differences between the strengths of the superior and inferior regions.
  • the collagen fibers are enmeshed in a ground matrix of glycosaminoglycans (GAG) such as keratan sulfate and chondroitin sulfates of varying degrees of sulfation. Both substances, but particularly chondroitin sulfate, are markedly hydrophilic and contribute to a negative intrastromal fluid pressure under which the entire stroma is heavily compressed. Intraocular pressure further compresses the stroma through its direct effect at the posterior surface and by its contribution to lamellar tension. The intrastromal pressure, often called the "swelling" pressure because of its tendency to draw water into the stromal ground substance, has been measured as -50 to -60 rnn Hg through a variety of in vitro and in vivo techniques.
  • GAG glycosaminoglycans
  • the cornea may imbibe additional water through the limbus as a result of the pressure difference between the perilimbal capillaries and the stromal interstitium. As one would expect, the swelling pressure diminishes as stromal hydration and thickness increase and a new steady-state is established.
  • peripheral stromal thickening and central flattening is the existence of a mechanical relationship between disrupted and intact lamellae.
  • lamellae are assumed instead to be structurally and mechanically independent of neighboring lamellae — that is, arranged in layers without any interconnections — then the severed peripheral segments are unable to bear or transfer any tension.
  • This is, in fact, a simplifying assumption incorporated into most numerical models of refractive surgery.
  • the tensile load previously borne by the full complement of lamellae is shifted to the remaining posterior fibers, which now strain (stretch) slightly under the concentrated stress.
  • the stretch may not be accomplished by an increase in corneal diameter and must therefore occur as central corneal bulging and anterior steepening.
  • the proposed peripheral response is considered, this occurs as a peripheral thickening and peripheral steepening with coincident central flattening.
  • the latter scenario aptly describes the characteristic peripheral "knee" and central flat zone of PTK, PRK and LASIK, finite element analyses of uniform thickness profiles have not incorporated the peripheral response and have predicted a corneal configuration opposite that produced clinically, hi short, consideration of the proposed peripheral stromal response and its mechanical relationship to the central cornea, as well as the negative intrastromal pressure, is critical not only for correctly predicting the magnitude of refractive correction, but in some cases, the direction.
  • the proposed biomechanical model predicts additional flattening over and above whatever ablation profile is programmed, whether myopic with an intent to flatten, hyperopic with an attempt to steepen, or nonrefractive PTK. This would theoretically make hyperopia a more difficult procedure, since the biomechanical flattening would be in opposition to the ablation profile, thus requiring a deeper ablation to offset the biomechanical response..
  • This prediction was verified in the first 8 patients treated with the Autonomous Custom Cornea, wavefront-guided ablation procedure. Of the 8 patients treated, 5 were myopic and 3 were hyperopic. Only the wavefront data were used to program the laser. Neither refraction, nor empirical experience were used.
  • primary hyperopic procedures require a treatment of up to 35% greater than the spherical equivalent, meaning greater than expected depth must be ablated to achieve the desired correction. This is consistent with the proposed model predicting biomechanical flattening, independent of the ablation profile. Greater depth must be ablated with a primary hyperopic treatment to overcome the biomechanical flattening which creates a surface shape effect opposing that of the ablation profile.
  • the secondary hyperopic group required substantially less depth of ablation to achieve the same level of correction as the primary hyperopia group. This is also completely consistent with the proposed biomechanical model.
  • the secondary post-LASIK hyperopic group already had an altered corneal structure with an associated biomechanical response from the first refractive procedure. In other words, there was less biomechanical flattening to overcome in the second procedure, thus requiring less depth of ablation for the same correction, since the biomechanical effect had already occurred in conjunction with the first procedure, as illustrated in Figure 13.
  • the secondary hyperopes had a more stable longer term refraction, with the primary hyperopes exhibiting slight regression over the 6 month post-operative follow-up period.
  • One possible explanation for this difference lies in the long-term healing related to the biomechanical effect, which would be exaggerated in the primary hyperopia group, as opposed to the secondary hyperopia group where the biomechanical effects had already occurred and were thus reduced.
  • Ablation depth was defined as preop - post- op, and epithelial depth was defined as Sx - post-op, recognizing that edema may have been a factor in the immediate post-op map.
  • Munger reported epithelial thickening at the ablation edge. However, an increase in the calculated epithelial measurement outside the ablation zone may be due to stromal thickening rather than epithelial, since the PAR CTS measures surface elevation and cannot distinguish between epithelial and stromal thickening.
  • Ablation depth is a more robust measurement than the much smaller epithelial thickness, and by 6 months the cornea should be relatively stable. Note that outside the ablation zone, there is negative ablation depth, or increased elevation compared to the pre-operative state. This provides indirect evidence of peripheral thickemng, an important feature of the proposed biomechanical model, with a different laser/topographer combination.
  • Sborgia, et al has reported results of a corneal topography guided system called Corneal Interactive Programmed Topographic Ablation (CIPTA). (Sborgia C, Alessio G, Boscia F, Vetrugno M. Corneal hiteractived Programmed Topographic Ablation: Preliminary Results.
  • CIPTA Corneal Interactive Programmed Topographic Ablation
  • LASIK is performed with a Summit Apex Plus using a Krumeich-Barraquer microkeratome to make the flap.
  • Corneal measurements are acquired pre and post-operatively with optical coherence tomography and the following corneal topographers for validation of effect: EyeSys, Humphrey Atlas, Keratron, Orbscan II, PAR, Technomed C-Scan, and TMS-1.
  • Average pre-operative refractive error of the small preliminary group is -6.875+2.03 diopters sphere + 0.8125+0.51 diopters cylinder.
  • Orbscan corneal topography data Only the Orbscan corneal topography data will be presented here.
  • the anterior tangential, anterior elevation and pachymetry data were exported to a customized topography tool for analysis and the cornea was divided into three regions: central 2.75 mm radius (5.5mm diameter), transition zone from a radius of 2.75 - 3.25mm (5.5-6.5 mm diameter), and outside the ablation zone from a radius of 3.25 - 4.5mm (6.5-9.0mm diameter).
  • the pre-operative topography was subtracted from the postoperative topography for the surgical patients, and the repeated measurements were subtracted for the normal subjects.
  • the elevation maps the two surfaces were fit within the 0.5mm transition zone.
  • average regional differences were calculated over the normal and surgical populations, and statistical analysis was performed using the ANOVA ("Analysis of Variance") procedure in the software package, (Statistical Analysis System, Cary, NC)
  • Figures 16 and 17 show the composite difference maps of all subjects for the normal and 1 day post-operative surgical groups, respectively. Significant (p ⁇ 0.05) decreases in elevation, pachymetry, and curvature in the central zone between normals and surgical subjects were demonstrated. In addition, significant (p ⁇ 0.05) increases in elevation, pachymetry, and curvature in the outer zone were found, as predicted by the proposed biomechanical model. These increases persisted at 1 month post-operatively, as seen in Figure 18.
  • Geometric bias was defined as either a myopic or hyperopic bias in the pattern of ablation zone thickness loss in order to investigate current shape-subtraction theories of hyperopic shift in PTK.
  • a second in vitro study was performed to further examine the relationship between peripheral stromal thickening and central flattening.
  • GTA topical glutaraldehyde
  • Each eye was individually mounted in a custom holder, inflated to normal intraocular pressure (15 mmHg) and deepithelialized.
  • one cornea of a given donor pair was immersed in a 15% dextran solution for 40 minutes then transferred to 4% GTA/dextran for an additional 20 minutes; the fellow control was exposed to 15% dextran for 60 minutes.
  • Each eye was subsequently subjected to 1) sham PTK, a same-eye control phase incorporated to account for thinning due to intraoperative dehydration, 2) PTK (5-mm-diameter, lOOum-depth) and 3) a 1-hour hypo-osmotic soak phase designed to assess the anti-swelling activity of stiOmal crosslinking.
  • a scanning-slit topography system (Orbscan) was used to acquire triplicate thickness and curvature measurements before and after each experimental phase.
  • OCT Optical coherence tomography
  • OCT is an imaging technology which has only appeared in the literature since the 1990s.
  • OCT images are analogous to ultrasound images, in that they are two dimensional cross sectional images depicting tissue reflectivity.
  • the images show infrared reflectivity and demonstrate a 10 micron longitudinal resolution, as compared to the 50 micron longitudinal resolution associated with traditional ultrasound.
  • high frequency ultrasound does allow a 20 micron longitudinal resolution, it cannot penetrate more than 4 mm beyond the cornea.
  • the OCT also is also hmited to 3 mm penetration.
  • the optically clear nature of the eye allows the retina to be imaged to a depth of 3mm.
  • the OCT offers additional advantages in that it is non-contact, unlike high frequency ultrasound which requires a water bath and topical anesthetic.
  • the principles by which OCT works are those of interferometry.
  • the OCT is essentially a Michelson interferometer with the subject's eye placed at the end of one of the light paths.
  • Corneal measurements following the cutting of the corneal flap (or other perturbation), but before ablation, are a key factor in embodiements of this invention.
  • the microkeratomic incision for the flap produces definite changes in the cornea, regardless of any subsequent removal of tissue.
  • the redistribution of strain caused by the keratomic incision causes the central cornea to flatten and the peripheral stromal matrix to thicken and become steeper. This reshaping assists with a myopic correction, i.e., a correction where increased corneal curvature is prescribed, and works against a hyperopic correction.
  • corneal topography, optical coherence tomography, ultrasound, refraction and/or wave front analysis is used both before and after the microkeratomic incision for the corneal flap (or other corneal perturbation), from a statistically sufficient number of subjects who may be surgical patients, and the differences compared to expected and achieved post-operative results (undercorrected or overcorrected).
  • comparison of the measurements before and after the incision will allow one to adjust the ablative procedure to account for the predicted biomechanical response, as a function of the changes measured after cutting the flap (or other corenal perturbation).
  • these adjustments are made by laser manufacturers to their laser algorithms.
  • this invention may also be practiced by developers of corrective tables for current laser systems, or by surgeons using such tables.
  • Ablation profile adjustments can be made in advance of the ablation in a separate procedure, or in real-time as an intraoperative adjustment, after the pertubation, but before the ablation.
  • corneal topography, optical coherence tomography, ultrasound, refraction, and/or wave front analysis are acquired both pre-operatively and post-operatively, after the laser refractive procedure, from a statistically sufficient number of subjects who are surgical patients.
  • the pre-operative data are used to partially define the specifications of individual biomechanical mathematical models of individual corneas (thickness profile, curvature profile, corneal size).
  • the ablation profile with which an individual was treated, is then used to mathematically "remove" layers from the model, and the post-operative data are used to define the final condition of the model.
  • PRK, LASIK, and LASEK would each require distinct mathematical models, since the tissue removed is distinctly located within the corneal stroma. (e.g. PRK and LASEK are surface ablations and LASIK is a deeper ablation.)
  • Knowledge of the pre-operative and post- operative state, measured from the subject allows the model properties (e.g. Young's modulus) to be adjusted in order to match the final predicted post-operative state achieved by the model with the actual measured post-operative state, in an iterative process.
  • the material properties thus determined for all corneas and all models within the subject population will be correlated with the pre-operative population data (e.g. age, sex, race, years of contact lens wear) and measured pre-operative data (e.g.
  • corneal topography, optical coherence tomography, ultrasound, refraction, and/or wave front analysis are acquired pre- operatively, both before and after the microkeratomic incision for the corneal flap (or other corneal perturbation), and post-operatively, after the laser refractive procedure, from a statistically sufficient number of subjects who are surgical patients.
  • the pre-operative data and are used to partially define the specifications of individual biomechanical mathematical models of individual corneas (thickness profile, curvature profile, corneal size).
  • the ablation profile with which an individual was treated, is then used to mathematically "remove" layers from the model, and the post-operative data are used to define the final condition of the model.
  • PRK, LASIK, and LASEK would each require distinct mathematical models, since the tissue removed is distinctly located within the corneal stroma. (e.g. PRK and LASEK are surface ablations and LASIK is a deeper ablation.)
  • Knowledge of the pre-operative, and post-operative state, measured from the subject allows the model properties (e.g. Young's modulus) to be adjusted in order to match the final predicted post-operative state achieved by the model with the actual measured post-operative state, in an iterative process.
  • the material properties thus determined for all corneas and all models within the subject population will be correlated with the pre-operative population data (e.g. age, sex, race, years of contact lens wear), measured pre-operative data (e.g.
  • pre-operative parameters both characteristic and measured
  • post-pertubation data to determine which pre-operative parameters (both characteristic and measured) and/or post-pertubation parameters best predict the material properties and thus response.
  • These correlations will be used to compile a program that will produce material properties as an output, with pre-operative and post-pertubation data as input.
  • the material properties program, along with individual pre-operative data and post-pertubation data will be used to fully define a predictive biomechanical model of individual response to corneal ablation. Model predictions will allow one to adjust the ablative procedure to account for the predicted biomechanical response, based on preoperative and post-pertubation data. Preferably, these adjustments are made by laser manufacturers to their laser algorithms.
  • this invention may also be practiced by developers of corrective tables for current laser systems, or by surgeons using such tables.
  • Ablation profile adjustments can be made in advance of the ablation in a separate procedure, or in realtime as an intra-operative adjustment, after the pertubation, but before the ablation.
  • the corneal healing response is characterized using OCT imaging to measure epithelial, stromal, and flap thickness. For each examination, five images are acquired in the vertical meridian and five in the horizontal meridian, until the remote site completes the software to scan the cornea in a radial spoke pattern covering the central cornea within an 8mm diameter.
  • the OCT examinations is performed at the same time points as the topographic measurements for comparison purposes: pre-operatively and post-operatively at one day, one week, one month, three months, and six months, with the addition of one time point immediately after surgery in order to visualize the flap interface.
  • the biomechamcal response is believed to be immediate, with modification through the healing phase. Therefore, the behavior of the model is defined based on one day, one week, one month, 3 months, and 6 months post-operative measurements, with the exception of the OCT measurements that will be taken immediately after the surgery in order to visualize the flap.
  • an optimization approach is used to design new ablation algorithms. Rather than providing an ablation profile to the model and predicting the corneal response, optimization criteria is used as input to produce the necessary ablation profile to meet the criteria. Examples may be to maximize ablation zone diameter, while minimizing ablation depth to reach a target central curvature with minimal aberrations.
  • Post-operative corneal shape is the function of at least three factors: the ablation profile, the healing process, and the biomechanical response of the cornea to a change in structure. Only by increasing our knowledge of the interaction of these factors can predictability in PRK and LASIK be improved. This has important implications in the development of new ablation algorithms and guided procedures. It points to an optimization approach, rather than a priori defining an "ideal" corneal shape that is ultimately not achievable. There are only certain shapes a cornea will biomechanically assume. For example, the deeper the peripheral cut in a myopic procedure to generate a potentially desirable post-operative "prolate" shape, the greater the number of severed lamellae and the greater the biomechamcal central flattening response to counter the effect.
  • step one is to gain a better understanding of comeal response to standard ablation profiles in well-controlled studies, before moving into the realm of customized procedures.
  • the outcome measures in these controlled studies should be more comprehensive than in the past to allow us to thoroughly interrogate the corneal response. This means we need to measure and report the outcome error in terms of the predicted topography and/or the predicted wavefront, not just visual acuity, spheres and cylinders.
  • each layer is reinforced by a number of long collagen fibers with the same direction.
  • the direction of the collagen fibers in each layer is different so that the in-plane reinforcement is more or less uniform.
  • the model is simplified not only because the number of layers is reduced from 300-500 to 7 but also because the collagen fibers are collectively assumed to be thin hard shell layers instead of maintaining individual long cylindrical shape.
  • This simplified model is significantly different from any existing comeal finite element model in the sense that the basic microstructure of the cornea as a layered or lamellar structure, along with being highly porous, is directly incorporated into the finite element model.
  • basic substances which make up the comea such as collagen fibers and ground substance (proteoglycans) and water are modeled separately.
  • Figure 25 a simple model for an ablated co ea after surgery relevant to PRK is presented. A part of the two outer layers (layer #1 and #2) is removed from the intact comeal model.
  • the overall material properties for both hard and soft layers are assumed to be linearly elastic and isotropic.
  • the elastic moduli are taken from the literature.
  • the soft layer is assumed to be a Mghly porous material. Based on the existing theories for fluid-filled porous materials (Katsube, 1985; Katsube and Carroll, 1987a,b), this porous material assumption requires additional elastic material parameter such as the bulk modulus of the solid matrix material of the soft layer without pores.
  • the physical measurement of the bulk modulus of the matrix itself (without pores) will be extremely difficult and has not been reported in literature.
  • this bulk modulus is assumed to be infinite, and the matrix itself (without pores) is assumed to be incompressible. This assumption is reasonable because the volume fraction of the matrix is extremely low in the cornea, and much of the volume compaction or expansion of the soft layers can be attributed to the pore space compaction or expansion through the deformation of the matrix.
  • volumetric expansion of a porous solid material due to the internal pore pressure is similar to volumetric thermal expansion due to temperature increase although the physical mechanisms are completely different. Therefore, this volume change due to the internal pore pressure can be replaced by the thermal expansion term in any of the commercially available finite element codes, provided the material properties of the (dry) porous material (without fluid) and those of the solid matrix (without pores) are known.
  • the negative ("imbibition") pressure of magnitude 60 mm Hg is applied uniformly throughout the pore boundary of highly porous layers #2, #4, and #6, in addition to the intraocular pressure of magnitude 15 mmHg applied on the posterior surface of the comea.
  • the commercially available finite element code ABAQUS with four-node axisymmetric elements is employed.
  • the negative ("imbibition") pressure is applied only to porous layer #4 and #6, and zero pore pressure is assumed in the centrally ablated or cut porous layer #2.
  • This simplified assumption is based on the fact that the fluid movement is most likely to occur in the in-plane direction rather than out-of-plane direction due to the layered nature of actual comea. Since the internal fluid is suddenly exposed to the atmospheric pressure at the place where the layer is severed, the internal pressure is set equal to zero in layer #2.
  • the contours of the spherical surface B (the interface between the soft layer #2 and the hard layer #3) for the intact comea model ( Figure 24) and ablated or cut cornea model (Figure 25) are plotted in Figure 26.
  • the displacements are magnified by a factor of 10 so that the comparison before and after the surgery can be visually observed.
  • the spherical surface B flattens after the surgery. This flattening due to the surgery demonstrates the same trend as the conceptual model, supported by clinically observed results described earlier in this application.
  • the overall comeal deformed shapes before and after the surgery are compared based on the two different approaches.
  • the overall co eal deformed shapes for the intact and ablated or cut corneal models are compared based on the fluid-filled porous material assumptions for soft layers.
  • the peripheral portion of the comea after ablation is thicker than that before ablation.
  • This peripheral thickening matches the conceptual model supported by clinical results, described earlier in this application, i Figure 29, the overall comeal deformed shapes between the intact and ablated or cut comeal models are compared based on the solid material assumptions for soft layers.
  • the peripheral thickening after ablation is not observed. Therefore, the existing simulations based on the solid material assumption are not consistent with clinical results after laser refractive surgery, described in this application.
  • this homogeneous "hydrated” solid material is in fact an "equivalent” homogeneous solid material, and this "equivalent” homogeneous solid material is actually highly heterogeneous in the sense that it contains pores and pores are filled with water.
  • porosity pore volume per unit volume of a porous solid material
  • the deformation due to the internal pore pressure which is missing in the existing methods, can be considered.
  • the volume expansion due to internal pore pressure can be simulated by mimicking thermal expansion due to temperature change.
  • this replacement can be done by knowing the overall material properties of the porous solid material (solid matrix and pore) and those of the solid matrix (without pores).
  • the co ea is highly porous, much of the overall volume change can be attributed to the change in pore space rather than the expansion or compaction of the solid matrix (without pores). Therefore, by employing the simplified assumption of incompressibility of the solid matrix (without pores), the expansion due to the given pore pressure can be simulated through thermal expansion terms. This leads to the direct incorporation of the negative (“imbibition”) pressure applied to the pore boundary of the highly porous comea. In this way, the existing simulations can be modified to include the effect of the position-dependent negative (“imbibition”) pressure inside the comea on the comeal biomehanical response to the surgery.
  • the hard layer representing the collagen fibers and the soft layer representing the matrix or ground substance and water are modeled separately.
  • this layered structure can be modeled as an "equivalent" homogeneous anisotropic material on the basis of the composite material models for layered structure by Katsube and Wu ("A Constitutive Theory for Porous Composite Materials," International Journal of Solids and Structures, Vol. 35, pp. 4587-4596, 1998).
  • Katsube and Wu A Constitutive Theory for Porous Composite Materials
  • deformation of the fiber and the ground substance and water inside the comea can be separated within the framework of a single, continuum model.
  • This homogenization technique can again be used as a tool to introduce more detailed micro-structure to the existing simulations. If the detailed information regarding the microstructure is introduced in the modeling, more detailed information can be obtained from simulations.
  • these processes of introducing more microstructure into modeling can also be achieved by simply carrying out several levels of macro-micro numerical simulations. For example, in the smallest scale level, local positional arrangement (orientation) of individual collagen fibers may be modeled, h addition, the reorientation and stretch of collagen fibers as well as undulation structure of individual collagen fibers can also be separately modeled.
  • These small-scale level models can be incorporated into the intermediate-scale level of layered structural model. The obtained intermediate-scale level model can further be incorporated into the large-scale boundary value problems of co eal deformation.
  • the simple finite element models based on this invention can predict the correct trend in comeal response to laser refractive surgery, as opposed to existing models in the literature.
  • a flap is first created by a microkeratome and then comeal ablation is performed. After ablation, the hinged flap will be replaced in its original position.
  • material properties relevant to the model can be back calculated from the biomechanical response of a comea due to the flap creation (but before ablation). The mechanical response due to ablation can then be simulated and the post-operative condition can be predicted based on the model simulations. This information can assist the physicians to make decisions about the operation before actual ablation. Therefore, this invention can be very useful in increasing the success rate of refractive surgery.
  • modeling, optimization and algorithm correction of the present invention may be achieved by written calculation or by implementation via a computer system.
  • Those skilled in the art of mathematical computer modeling, computer programming, and database manipulation and administration will readily appreciate that the methods and systems described herein may be software based and may be performed by a computer system.
  • a computer comprising a central processing unit, a storage medium (such as a magnetic hard drive), a display device (such as a monitor) and an input device (such as a keyboard and/or a mouse) may be used to perfonn. the methods of the present invention.
  • Pre-operative and post-pertubation measurements are inputted to the computer system by keystroke or by other similar methods, including direct data transfer of measurements inputted into another computer or similar machine.
  • Existing algorithms for ablative procedures may be inputted in digital form by any appropriate method. Additional empirical, deterministic or other data may be inputted to the computer by any appropriate method.
  • Data inputted into the computer is stored by any appropriate method, including readonly memory (RAM) or other storage devices, such as a hard disk drive. Analysis and comparison of inputted and/or stored data items is achieved by implementing appropriate software algorithms on the computer which compare the relative values of stored data. Adjustment of existing algorithms for ablative procedures is achieved by retrieving a ablative procedure from data storage and modifying it. The modified algorithm is restored or implemented during surgery.
  • Data derived or created by the present invention is stored in a computer by any appropriate method, including storage on an appropriate computer readable medium.
  • An example of an appropriate computer readable medium is RAM or a magnetic hard drive. Depending upon the nature of the data, the data may be stored in a table or other appropriate data structure on such a computer readable medium.
  • a computer system implementing a method of the present invention may be used during comea surgery. Data may be inputted to such a computer system during the surgical process, and the computer system outputs responsive data during the surgery. For example, a surgeon or other personnel at surgery inputs pre-operative measurements into the computer. The computer, implementing the present invention, determines specifications for ablation based upon such measurements.
  • post- pertubation measurements are acquired by diagnostic devices (comeal topography, wavefront analyzer, optical coherence tomography, ultrasound) which are integrated with the laser to allow all measurements to share a common reference axis.
  • diagnostic devices component topography, wavefront analyzer, optical coherence tomography, ultrasound
  • These data are inputted into the computer via the integrated system.
  • the computer determines adjusted specifications for ablation, and outputs such adjustments to the surgeon.
  • the surgeon implements the ablation with the adjusted specifications.
  • a computer system implementing a method of the present invention may also be used prior to co ea surgery to create a biomechanical model based upon inputted data.
  • a computer system implementing a method of the present invention may also be used subsequently to comea surgery to collect data from the surgery to be used in biomechanical modeling.
  • corneal biomechanics including the reshaping of the cornea that results from a microkeratome incision, the reshaping of both the central area of the comea and the surrounding peripheral area that results from ablative surgery, and the reformation produced by post-operative healing must be accounted for to establish truly customized ablative procedures for individual patients.
  • Current ablative algorithms do not adequately reflect these biomechanical factors.
  • surgical results to date have frequently fallen short of achievable optimum goals. Fortunately, however, manufacturers of diagnostic and surgical equipment, such as comeal topographers, optical coherence tomographers, wave front analyzers and lasers, and surgeons, can account for these factors using the procedures and instruments described herein.
  • 20/40 visual acuity with plus or minus one diopter of residual refractive air should no longer be acceptable results for LASIK regular or PRK regular surgery.
  • 20/20 or even 20/10 visual acuity, with minimal aberration, should be achievable with most patients.

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Abstract

Des réactions biomécaniques de l'oeil sont utilisées en vue d'améliorer les procédures photoréfractives. Les traitements LASIK ou PRK, par exemple, peuvent être améliorés en prenant des mesures pré-opératoires et en prévoyant la réaction biodynamique de la cornée au traitement ablatif. L'utilisation prévisionnelle découle de la réaction biodynamique de la cornée au laser ou à la kératectomie mécanique, à savoir, de la création d'une caractéristique du lambeau cornéen du LASIK. La comparaison entre le lambeau avant et après, les données (de pré-ablation) de la cornée telles que l'épaisseur de la cornée, l'épaisseur du lambeau, la topographie de la cornée et le front d'ondes, par exemple, peuvent fournir des informations prévisionnelles applicables en vue de modifier l'algorithme d'ablation avant d'utiliser le laser, soit pour une opération réel soit pour le développement d'un modèle. La modélisation, par analyse d'élément fini ou d'autres techniques mathématiques, peut également être utilisée en vue de prévoir les résultats post-opératoires fondés sur les données pré-opératoires (pas de coupe de lambeau ou autre intervention chirurgicale) de la cornée lesquels sont entrées pour un modèle d'oeil précis qui, en prenant en considération la réaction biodynamique ∫i⊃via∫/i⊃ le modèle, fournit des informations prédictionnelles destinées à améliorer le succès de la chirurgie réfractive et par là même la satisfaction du patient.
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CA2416598A1 (fr) 2002-01-31
WO2002007660A2 (fr) 2002-01-31

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