CA2216205A1 - Segmented intrastromal corneal insert for altering corneal refractive properties and methods thereof - Google Patents

Abstract

An intrastromal corneal insert for effecting a change in the corneal curvature to treat conditions such as astigmatism myopia, and hyperopia. The insert includes one or more arcuate or arc-shaped segments.
The extent of corneal correction by such a segment, for a given cross-sectional configuration, is a function of one or more predefined parameters, including the arc angle, radius of curvature, cone angle, modulus of elasticity, and thickness of the segment. The invention also provides for various methods for changing the refractive characteristics of an eye. Generally, the methods involve determining the amount of corrective refraction desired, providing an intrastromal channel which traverses at least a portion of the circumcorneal rotation, and introducing one or more of the inventive segmented inserts.

Description

SEGMENTED INTRASTROMAL CORNEAL INSERT FOR AI,TERING
COR~IEAL REFRACTIVE PROPERTIES AND METHODS THI~REOF

Technical Field S The present invention relates to intrastromal corneal inserts and methods for altering refractive properties, including the corneal curvature and/or the aspheric shape, of the cornea of an eye. More specifically, the invention involves intrastromal corneal segments having various predefined parameters, including but not limited to arc angle, radius of curvature, cone angle, thickness, and width, which effect this change when the segments are inserted into the cornea. The invention also involves methods for inserting one or more of the segments into the cornea of the eye.
l~ck~rolln~l of the Invention Anomalies in the overall shape of the eye can cause visual disorders. Hyperopia ("f~r.si~hte~ln~cc.") occurs when the front-to-back distance in the eyeball is too short. In such a case, parallel rays origin~ting greater than 20 feet from the eye focus behind the retina. In contrast, when the front-to-back distance of eyeball is too long, myopia ("nearsightedness") occurs and the focus of parallel rays çnt~rin~ the eye occurs in front of the retina. ~cti~m~f;cm is a condition which occurs when the parallel rays of light do not focus to a single point within the eye, but rather have a variable focus due to the fact that the cornea refracts light in a different m~ri~ n at different ~lict~n~es. Some degree of asti~m~t;~m is normal, but where it is pronounced, the astigmZlfi~cm must be corrected.
Hyperopia, myopia, and actigm~ficm are usually corrected by glasses or contact lenses. Surgical methods for the correction of such disorders are known. Such methods ~nclucIc ~adial l~e~t~tQ.my (~g, U.S. Patcn~ No~ 4,815,463 ar.d 4,688,57Q3 ~ l~cer corneal ablation (see, e.g., U.S. PatentNo. 4,941,093).
Another method for correcting those disorders is through the implantation of polymeric rings in the eye's corneal stroma to change the curvature of the cornea. Previous work involving the implantation of polymethylmethacrylate ~PMMA) rings, allograft corneal tissue, and hydrogels is well documented. One of the ring devices involves a split ring design which is inserted into a channel previously dissected in the stromal layer of the cornea A minim~lly invasive incision is used both for producing the channel and for inserting the implant. See, for instance, the use of PMMA intrastromal rings in U.S.

Patents Nos. 4,452,235 to Reynolds, 4,671,276 to Reynolds; 4,766,895 to Reynolds; and 4,961,744 to Kilmer et al.
Adjlle~nent of intracorneal rings to obtain the necessary correction of the eye normally typically involves an adjustment of ring size or diameter. For example, U.S.
Patent No. 4,452,235 describes a method and an ~pa.dllls for corneal curvature adiustment by means of adjusting the diameter of the ring. The method involves inserting one end of a split end adjusting ring into the cornea of the eye and moving the ring in a circular path until its ends meet. The ends are thereafter adjusted relative to each other until the shape of the eye has assurned a desired curvature whereupon the ends are fixedly ~t~-~hf d to ms~int~in the desired curvature of the cornea.
Another manner in which intracorneal rings are adjusted for selectively correcting abnormalities of the eye involves varying the thickness of the rings. U.S. Patent No.
5,318,047 discloses a method that allows for the refractive correction of the eye by ~l~te., ~ -g the amount of correction necessary, selecting an intrastromal corneal ring of al.~ro~r;ate thickness to obtain the necessary correction from a selection of rings of varying thickness, and inserting the ring into the corneal stroma.
U.S. PatentNo. 5,405,384 also discloses an intrastromal intracorneal rings having varying thicknesses for the purpose of creating ast;gm~ti~m These rings have at least one region, and often have two or more regions, in which the cross section is thicker or the bulk of the region is more pronounced. By proper sllignm~ont of the larger regions of the ring with the eye's anomalies, the a~ti~m~ m can be alleviated.
Prior art intracorneal ring implants require forming a continuous circumferential çh~nnel within the stroma of the cornea, and thereafter inserting a continuous circular device therein. Such a requirement has important drawbacks. Forming a single, continuous channel at a constant or otherwise desired depth from the anterior surface of the cornea is surgically more complicated and necessitates additional steps to ensure that the channel is at a proper depth. Another drawback of continuous ring inserts is that, after insertion, they remain ;n contact with the initial surgical incision made ;n the cornea. The ring exerts pressure on the incision, making it more difficult to successfully suture the incision and increasing the possibility of post-surgical infection and reducing the rate of healing. Further, as the flow of nutrients occurs by diffusion from the posterior to the CA 02216205 l997-lo-os WO 97/~87S9 PCT/US97/01411 anterior side of the cornea, post-surgical contact between the insert and the incision site impedes the flow of nutrients to the incision site.
Instead of preforrned ring inserts, other prior art techniques for correcting visual aberrations include the use of a settable polymer or polymer gel. For example, U.S. Patent No. 5,095,955 suggests forming an intracorneal ring by introducing a settable polymer or gel into an intrastromal channel which has been previously made, and allowing t_e polymer to set. This procedure does not allow the surgeon to specify the precise shape of the resulting ring. Moreover, since the shape and length of the gel conforrns to that of the intrastromal channel, the gel insert cannot be rotated or moved within çh~nnel Thus, there is a need for an intrastromal corneal insert which overcomes the limitations of prior art inserts. In view of the particular limitations identified above, there is a need for an intracorneal insert which subtends less than 360~. Furthermore, there is a need for an intrastromal corneal insert that has an arc length and angle less than that of the insertion channel. In addition, it is desirable that such a segment have ~imen~ions (e.g, cone angle, thickness, cross-sectional area, arc leng~, etc.) which vary or are variable between portions of the segment to allow a surgeon to precisely control the ~limen~ions of the insert in order to achieve the desired corneal correction. It is also desirable to provide an assemblage of such segment~ having ~iimen~ions which vary from segment to segment.
Additionally, it is desirable to have a segment and a method of inserting the segment at a desired orientation or angle with respect to the cornea which provides for precise corneal adjustment irrespective of the thickness, width, or arc angle of the segment. Moreover, it is contemplat~d that the desired segments be used to introduce therapeutic or diagnostic materials into the cornea.
Sllmm~ry of the Jnv~ntion The present invention is directed to an intrastromal corneal insert for effecting a change in the corneal curvature to treat conditions such as asti~m~ticm~ myopia, and hyperopia. The insert is an arcuate or arc-shaped segment. The extent of cornealcorrection by such a segment, for a given cross-sectional configuration, is a function of one or more predefined parameters, including the arc angle, radius of curvature, cone arlgle, modulus of elasticity, width and thiclcness of the segment. Particular visual disorders, such as astip;m~ti~m~ myopia, hyperopia, and asti~m~ti~m in combination with either myopia or hyperopia, are correctable hy use of these segments.

CA 022l6205 l997-lO-09 WO 97/2~759 PCT/US97/01411 An aspect of the invention is to effect a change in the curvature of the cornea by providing one or more segments having a selected arc angle and radius of curvature.
~ segment of the present invention may also be provided with a mi~m~tching cone angle selected, independently of the segment's size, to impart an additional correction to 5 the corneal tissue when the se~ment is positioned at the desired location in the cornea.
More specifically, the mi5m~t-~hin~ cone angle can indep~n~lently effect a change in the radius of ~;Ul valule and/or the aspheric shape of the cornea can be effected. Thus, the cone angle is chosen based on the change of ~u- v~ e desired, the starting ~;ul v~Lule of the eye, and based on the thickness, radius of ~;w v~ , and modulus of elasticity of the segment 10 for a given cross-sectional configuration. The cone angle may be selected to change the curvature of the eye, and to either ~ or alter its original aspheric shape.Still another aspect of the invention is to effect a change in the Cul v~Lul~ of the cornea by providing segments of varying thickness and widths or ~ltern~t~ly, varying the thickness of portions of an individual segment The segm~nt~ may be used in isolation, in 15 isolated mllltiples, in coop~ldlive multiples, as segmen~ in a larger assemblage encircling at least a portion of the cornea, or as assemblages to form con~LI ucl~ of varying thickness.
The arcuate inserts have sufficient structural integrity to applo~ a~ the shape of some portion of the intrastromal channel into which a segment is to be placed. The segments may be comprised of one or more polymers having a high andlor low modulus of 20 elasticity. Segments having mi~m~tehed cone angles over at least a portion of their lengths are required to have a mil..lllu,~l flexural modulus of elasticity of about 3,500 psi, so that the segm~nt retains its ability to exert a micm~tohed cone angle effect over time. The inserts may further comprise a hydrophilic or hydrophobic m~teri~l, or may be a hybrid device comprising layered materials. The insert may have an inner portion or be hollow or 25 adapted to be fillable with a biologic agent, drug or other liquid, em~ ified, or time-release eye treatment or diagnostic m~tlori;~l, or gel or settable polymer.
When the insert is a hybrid, both the inner and outer portions may comprise variously one or more high or low modulus, physiologically compatible polymers or a composite of a low modulus polymer and a high modulus polymer. The inner portion may 30 comprise a gel or a polymeric material which is polymerized in situ after introduction into a hollow center layer.

CA 02216205 lsg7-lo-os Wo 97/28759 PCT/US97/01411 If hydratable polymers are used, they may be hydrated before or after introduction into the intrastromal passageway created by the surgical device used to introduce these devices into the eye. If the insert is made of a hydratable polymer and the outer layer is hydrated before insertion into the eye, the final size of the insert will be set before insertion. If the hydratable polymers are allowed to hydrate within the corneal space, the device (if a~plupliate polymers are chosen) will swell within the eye to its final size. If prehydrated, the outer layer often provides a measure of lubricity to the device, allowing it to be irlserted with greater ease.
Yet another aspect of the present invention is the use of various methods or techniques for rh~n~in~ the refractive characteristics of an eye. Generally, the techniques involve det~ . . .~; . .; l~ ~e amount of corrective refraction desired, providing an intrastromal channel which kaverses at least a portion of the circumcorneal rotation, and inkoducing one or more of the above described inventive segm~nt~ inserts. Specific indications, such as astigm~ti~m~ may be rectified by insertion of one or more of the inserts into a partial inkastromal channel to flatten the steeper portions or to steepen the flatter portions or to ~;mlllt~neously flatten and steepen portions of the anterior corneal surface without insertion of a complete intracorneal ring.
The above is a brief description of sorne of the features and advantages of the present invention. Other features, advantages, and embo(1iment~ will be aL,~a,el,t to those skilled in the art from the following description, accol"~anyillg drawings and appended claims.
Rrief Des~ tion of the nrawin~
Fig. 1 is a srhem~tic representation of a ho,i~on~l section of the eye.
Fig. 2 is a schem~tic illustration of the anterior portion of the eye showing the various layers of the cornea.
Fig. 3 is a schematic representation of an eye showing the average corneal curvature radius and aspheric shape of the cornea.
Fig. 4 is a schematic ieprese~ lion of a hyperopic eye showing the average corneal curvature radius and the aspheric shape of the cornea.
Figures 5A and SB show respectively a front view and a cross section of a typical intracorneal insert made according to the invention.

CA 0221620~ 1997-lO-09 Fig. 6 is a diagr~mm~tic cross-sectional view of a cornea showing an im~g;n~ry intracorneal ring positioned therein having a m~tchin~ cone angle and illustrating geometric relationships of the im~in~ry ring relative to the cornea.
Figs. 7 and 8 illustrate geometric relationships between a mi~m~tching segment and S a cornea in accordance with the present invention.
Fig. 9 illustrates another embodiment of the present invention in which one segment is provided with multiple cone angles.
Fig. 10 is a sectional view taken along line 10-10 in Fig. 9.
Fig. 1 1 is a sectional view taken along line 11-1 1 in Fig. 9.
Fig. 12 illustrates a further embodiment of the present invention in which two segments are provided with multiple cone angles.
Fig. 13 is a cross-sectional view of a cornea showing segments of the present invention positioned therein and having m~tching cone angles.
Fig. 14 is a cross-sectional view of a cornea showing segment~ of the present invention positioned therein and having mi~m~tc~hing cone angles that according to one embodiment of the invention effects the fl~tt~nin~ of the corneal anterior surface for treating myopia.
Fig. 15 is a cross-sectional view of a cornea showing segm~t~ of the present invention positioned therein and having mi~m~tçhing cone angles that according to another embodiment of the invention effects the steepening of the corneal anterior surface for treating hyperopia.
Fig. 16 is a frontal view of segments of the present invention having symmetrical areas of added bulk or cross-section.
Fig. 17 shows a segment of the present invention in which the thickness of the segment is varied.
Fig. 1 8A-C show respectively a front view, a cross-section, and a top view of an embodiment of a segment made according to the present invention.
~ig. 1 9A-C show respectively a front view, a cross-section, and a top view of another embodiment of a segment made according to the present invention.
Fig. 20A-C show respectively a front view, a cross-section, and a top view of another embodiment a segment made according to the present invention.

CA 02216205 lss7-lo-os Fig. 21~-C show respectively a front view, a cross-section, and a top view of another embodiment a segment made according to the present invention.
Fig. 22A-C show respectively a front view, a cross-section, and a top view of another embodiment a segment made according to the present invention.
Fig. 23A-C show respectively a front view and two cross sections of a soft, filled intracorneal insert made according to the present invention.
Fig. 24 depicts a front view of an end-to-end assemblage of intracorneal segments having no end junctions between the segment~- junctions between the inserts to hold them in a particular spatial relationship.
~ig. 25 shows a ~ont view of an end-to-end assemblage of intracorneal segments having junctions bet~,veen the inserts to hold them in a particular spatial relationship.
Fig. 26 shows a partial cross-sectional view of an end-to-end assemblage of intracorneal segments which are strung on a fil~m~nt to form a ring.
Fig. 27A and B show respectively a front view and a cross section of an assemblage of intracorneal inserts made according to the invention which overlap at their ends to form a single monolithic device.
Fig. 28A-E schematically depict steps of a procedure for in~t~llin~ the intracorneal segmenf~ of the present invention.
Fig. 29A-E schem~tic~lly depict steps of another procedure for in~st~llin~ the intracorneal segments of the present invention.
Detailed nescription of the Invention Prior to explain~ng the details of the inventive devices and methods, an explanation of the physiology of the eye is provided in conjunction with Figs. 1-2. Referring to Fig. 1, a horizontal section of the eye is shown. Globe 1 1 of the eye resembles a sphere with an anterior bulged spherical portion representing cornea 12. Globe 11 of the eye consists of three concentric coverings enclosing the various transparent media through which the light must pass before reaching the sensitive retina 18. The outermost covering is a fibrous protective portion the posterior five-sixths of which is white and opaque and called the sclera 13, and sometimes referred to as the white of the eye where visible to the front. The anterior one-sixth of this outer layer is the transparent cornea 12.
A middle covering is mainly vascular and nutritive in function and is comprised of the choroid 14, ciliary body 16 and iris 17. Choroid 14 generally functions to maintain CA 0221620~ 1997-10-09 retina 18. Ciliary body 16 is involved in suspending lens 21 and accornmodation ofthe lens. Iris 17 is the most anterior portion of the middle covering of the eye and is arranged in a frontal plane. It is a thin circular disc corresponding to the diaphragm of a camera, and is perforated near its center by a circular aperture called the pupil 19. The s;ze of the pupil S varies to regulate fhe amount of light which reaches retina 18. It contracts also to accornmodation, which serves to sharpen the focus by ~limini~hin~ spherical aberration.
Iris 17 divides the space between cornea 12 and lens 21 into an anterior chamber 22 and a posterior chamber 23. The innermost portion of covering is retina 18, coneiefing of nerve elements which form the true receptive portion for visual hl,plessions.
Retina 18 is a part of the brain arising as an outgrowth from the fore-brain, with optic nerve 24 serving as a fiber kact connecting the retina part of the brain with the fore-brain. A layer of rods and cones, Iying just beneath a pigm~nt~cl epithelium on the anterior wall of the retina serve as visual cells or photoreceptors which kansform physical energy (light) into nerve impulses.
Vitreous body 26 is a l,d,lsl,alc.ll gelatinous mass which fills the posterior four-fifths of globe 11. At its sides it ~iU~J~JOll~ ciliarv body 16 and retina 18. A frontal saucer-shaped depression houses the lens.
Lens 21 of the eye is a ll~ls~alt;lll bi-convex body of crystalline appearance placed between iris 17 and vitreous body 26. Its axial diameter varies m~rke-lly with 20 accommodation. Ciliary zonule 27, consisting of transparent fibers passing between ciliary body 16 and lens 21 serves to hold lens 21 in position and enables the ciliary muscle to act on it.
Referring again to cornea 12, this outerrnost fibrous ll~a~ n~ coating resembles a watch glass. Its curvahlre is somewhat greater than the rest of the globe and is ideally 25 spherical in nature. However, often it is more curved in one meridian than another giving rise to ast;~m~ti~m The central portion of the cornea is called the optical zone with a slight fl~tt~ning taking place outwardly thereof as the cornea thicl~ens towards its periphery. Most of the refraction of the eye takes place through the cornea.
Referring to Fig. 2, a more detailed drawing of the anterior portion of the globe 30 shows the various layers of cornea 12 comprising an epithelium 31. Epithelial cells are rich in glycogen, enzymes and acetylcholine and their activity regulates the corneal corpuseles and controls the transport of water and electrolytes through the lamellae of the stroma 32 of cornea 12.
An anterior lirniting lamina 33, referred to as Bowman's membrane or layer, is positioned between the epithelium 31 and stroma 32 of the cornea. Stroma 32 is 5 comprised of larnella having bands of fibrils parallel to each other and crossing the whole of the cornea. While most of the fibrous bands are parallel to the surface, some are oblique, especially anteriorly. A posterior limitin~ lamina 34 is referred to as Descemet's membrane. It is a strong membrane sharply defined from stroma 32 and resistant to pathological processes of the cornea.
Endothelium 36 is the most posterior layer of the cornea and consists of a single layer of cells. Endotheliurn cells function to m~in~in the lrdl~s~ lcy of cornea 12.
Limbus 37 is the transition zone between the conJunctiva 38 and sclera 13 on the one hand and cornea 12 on the other.
Fig. 3 shows the globe of the eye having a cornea 12 with an average spherical radius of culv~ e 41 and a positive aspheric shape. By "average spherical radius of curvature" we intend the radius of the circle defined by the points at the periphery 45 of the cornea near the limbus of the eye and having a center 46. By "positive aspheric shape" we mean that the distance 47 from that center 46 to the anterior center of the cornea is greater than the average spherical radius of curvature, that is, the anterior surface of the cornea flatte~Ls as it progresses from the center 44 to its periphery 45. As shown in Fig. 3, when parallel rays of light pass through the corneal surface, they are refracted by the corneal surfaces to converge eventually near retina 18 of the eye. The diagram of Fig. 3 discounts, for the purposes of this discussion, the refractive effect of the lens or other portions of the eye.
The eye depicted in Fig. 4 is hyperopic because the light rays from the periphery of the cornea refract into focus at a point behind the retinal surface. Further, the eye depicted in Fig. 4 has does not have the same aspheric shape as that shown in Fig. 3. Distance 47 from center 46 to the anterior surface of the cornea is about the same as or less than the average spherical radius of .;uL v~ e 41 and the cornea does not flatten from center 44 to periphery 45 but rather plateaus or even dips at its center. If an intracorneal segment with a flat mi~m~t~hed cone angle, according to the present invention and as will be described in detail below, is implanted into the cornea shown in Fig. 4, the light rays refracted by the CA 0221620~ 1997-lO-09 now steepened corneal surface will be refracted at a larger angle and thus converge at a more near point such as directly on the retina. Further, selection of an intracorneal segment having a mi~m~tched cone angle may allow for the eye to obtain a more positive aspheric shape similar to that shown in the Fig. 3 eye.
S With the background ~ c~ ion of Figs. 1-4 in hand, it should be understood that the device and method of the present invention is for the adj-l~tment of at least a portion of an armular chord of the cornea to hllL.l- ve the vision of the eye. According to the present invention, one or more arcuate polymeric segment~ having predefined arc ang~es, radius of , matching or mi~m~tt~hin~ cone angles, thiclcnesses and/or widths, and modulus of elasticity, or combinations thereof for ch~ngtng the refractive properties of an eye. Each of the inventive aspects of the segments is discussed in detail below.
For purposes of ~ c~ ing the arc length or arc angle of the seginents of the present invention, and how variations in these parameter effect the shape of a cornea, Figure 5A
shows a front view of a typical insert made according to the invention and Figure SB
shows a cross section of that insert. As is shown in Figure 5A, the arcuate segment 100 is a portion of the circle and subtends some specific amount of a circumference of the cornea (at some chosen radius) equal to a value of "a" or "arc angle." The particular arc angle value is selected based upon the indication to be corrected and upon the particular configuration of the segment ~or segments) used. The arc angle is related to the arc length (La), the ratio of arc length to arc angle being defined by the t;2~les~ion La 2~RCC X (a/360~), for a given radius "r" of a segment For definitional purposes, the opposite ends of a single segment do not meet andsubtend less than 360~ when the segment is inserted into an intrastromal channel.
However, if two or more segments are joined or used in conjunction with each other, the sum of the values of "a" may be any of a wide range of values up to and including 360~. It should be noted that when a group of segment~ is used having a sum of arc angles equal to or greater than 360~, the advantage of not having the segm~nt in contact with the corneal entry incision is lost.
Another important parameter of the segments of the present invention is the radius of curvature (RCC~) The radius or radius of curvature of a segment is related to the rate of change of its curve relative to a fixed axis, or in other words, is related to the radius of the ring that can be configured from that particular segment. Selection of the radius of CA 02216205 1997-lO-09 curvature for a particular segment is dependent upon the segment's design and shape, the correction to be effected, and the radius of the channel formed in the cornea. For the majority of vision problems to be treated, the radius of curvature of a segment of the present invention which is inserted circumferentially about the cornea is between about l.S
rnrn and 4.25 mm.
Referring now to Fig. 5B, there is shown a radial transverse section of segment 100 having a hexagonal cross-sectional shape, one of a variety of suitable cross-sectional shapes for the segments of the present invention. The thickness of the segment, de~i~n~tecl with reference character "t", is generally between about O.OS mrn to 0.48 mm, and preferably bet~,veen about O.lS and 0.45.
Although a particular segment configuration has been described above, segments of other cross-sectional shapes, including but not limited to ovaloid and rectangular shapes, also may be used provided their respect*e ~ x;l~ radial transverse cross-sectit n~l rlime~ions are ~,vithin the allowable ranges defined above. Illustrative examples of other suitable shapes are discussed in more detail below.
Retllrnin~ to Fig. SB, for purposes of describing the cone angle(s) of the segments of the present invention, reference is made to an im~in~ry or phantom ring 102 having cross-sectional shape and thickness ~limen~ion~ identical to those of the segment to be inserte:d, and having a diameter configured from the segment having phantom ends which extendl to meet each other. The radial transverse cross-section of the segment is the cross-section that would cut through the diameter of such an im~gin~ry ring 102 superimposed on the insertion site. As sho~n in Fig. SB, the components of the radial transverse cross-section of im~gin~ry ring 200 are the cross-sectional area of segment 100 and phantom portion 104 (shown in phantom).
The cone angle ~ of im~ginZlry ring 102, and thus segment 100, is defined, for exarnple, as the angle between the plane of the flat surface 50 that im~gin~ry ring 102 rests on and a line drawn between points 52 of the cross-section that rests on the flat surface and point 54 on the cross-section that is farthest from the point where im~gin~ry ring 102 rests on the flat surface. In other words, cone angle ~ the angle formed between the major axis of a radial, transverse cross-section (e.g., axis 56 as shown in Fig. SB) and surface ~0.
Alternatively, cone angle 0 can be defined with reference to the angle formed by the intersection of major axes 56, angle ~, where ~ = (180-~)/2.

CA 022l6205 l997-lO-09 Referring to Fig. 6, an im~gin~ry ring, such as im~gin~ry ring 102 configured from segment 100 described above, is shown inserted into cornea 12. Tm~gin~ry ring 102 is shown having a cone angle m~t~he<l to the corneal archit~ctllre prior to insertion. A
m~trhing cone angle of a egment can be described with respect to the cone angle of im~gin~ry ring 102. A matched cone angle of im~gin~ry ring 102 may generally be considered to be one that m~tc.hes the angle defined by a particular line 62 that is tangent to the anterior surface of the cornea 12. That tangent line 62 is obtained by radially projecting the line 66 that extends along the major axis 56' of a radial, transverse cross-section of im~gin~ry ring 102 (e.g., along the line indicating ~lim~n~ion "w" in Fig. 5B) to the anterior corneal surface of the cornea. The major axis 56' of subst~nti~lly any kansverse cross-section of im~gin~ry ring 102 would be parallel to a line in the same plane as that major axis and tangent to the anterior surface of the cornea 12 where the line 64 that bisects the major axis line 66, and is perpendicular thereto, intersects the anterior surface of the cornea. The major axis line 66 is defined as the line which (1) exten~ls along the major axis 56' and (2) is bounded by the outer surface of the segment ~ m~tc.hing cone angle may vary according to changes in corneal shape and to the radial dimension of the segment used.
Conversely, a mi~m~trhin~ cone angle of im~inslry ring 102 is one in which the major axes 56' of substantially any radial, transverse cross-section of im:~gin~ry ring 102 would not be parallel to tangent line 66 at the point where bisecting line 64 isperpendicular to major axis line 66 and intersects the anterior surface of cornea 12.
Referring now to Figs 7 and 8, the concept of a mi.~m~tchin~ cone angle of a segment will be described in detail with reference to im~gin~ry ovaloid intracorneal rings (102', 102") superimposed at the insertion site prior to insertion ofthe cornea. These im~gin~ry rings have dimensions equal to those of the respective segments to be inserted.
As shown in the drawings, the major axis (axes 150 and 152 in Figs. 7 and 8, respectively) of substantially any radial, transverse cross-section of the ring (segment) are not parallel to a line (lines 160 and 162 in Figs. 7 and 8, respectively), which is in the same plane as the major axis and is tangent to the anterior surface of the cornea at the point where the line (line 170 and 172 in Figs. 7 and 8, respectfully) that bisects the major axis line (defined as the line extending along the major axis and bounded by the outer surface of the ring (segment)) and is perpendicular thereto, intersects the anterior surface of the cornea.

Alternatively, matching cone angles, and thus mi~m~tchin3~ cone angles, can be described relative to an equation. In deriving such an equation to calculate m~tçhin~ cone angles, applicants considered the variables listed below to be important in d~ .illg the 5 corneal radius change, ~Ros, achieved by implanting the ring in the cornea.
.

~Ros = J~ , t, d, Dj, R~c, Ey) where Rj = initial corneal radius of curvature (measured along the anterior corneal surface) (see, e.g, Fig. 6B) ~ = cone angle of the segment t = segment thickness d = depth of the segment in the cornea measured radially from the anterior corneal surface to the midpoint of a radial line, ext~n-ling across ~e thickest or largest radial dimension ~e.g, "t" in Fig. 5B) of the radial, transverse section referenced above 15 with respect to DCC (def~ned below) and shown, for example, in Fig. 6 where the depth is indicated with reference character "r".
Dj = limbus diameter 1~ = radius of curvature of the segment, where RCC = DCC /2 or one half of the diarneter of an im~gin~ry intracorneal ring configured from the segm-qnt to be inserted 20 (measured center to center, where each center is at the rnidpoint of the major axis line of a radial~ transverse section of the im~gin~ry intracorneal ring. Such centers are shown in Fig. 6, for example, where they are indicated with reference character "c").
Ey = Young's modulus for the segment 05 = segment cross-sectional area shape factor, which is a function of the 25 ration of LXA to CXA, or LXA
f ~

CXA

where LXA is the long axis of the radial, transverse cross-sectional area of 30 the segment and CXA is the circumference of the radial, transverse cross-sectional area of the segment.

These variables are believed to be the dominant ones that will indicate how the segment will perform in ch~nging corneal curvature or shape CA 02216205 1997-lO-09 In general, with a high Young's modulus, an increase in cone angle provides an increase in the minus correction which means an increase in the fl~tt~ning of the cornea.
By lowering the cone angle, one induces a positive correction which results in steepening the cornea. l\~r~t~hing the cone angle is dependent on the starting radial curvature of the 5 cornea. ~Rt is the expected radius of corneal curvature change in(ll~c e/l by segment thickness independent of cone angle for a given transverse, cross-sectional shape of any particular design where the change is measured as the initial radius of corneal curvature (i.e., the radius of curvature of the cornea prior to segment implantation) minus the final radius of corneal curvature (i. e., the radius of ~ e of the cornea after segment 10 implantation).
Further exarnples indicating that increasing the cone angle increases refractivecorrections are provided ~,vith respect to data obtained from tests conducted on human eye bank eyes. Cone angles of 31~ and 43~ provided refractive corrections of about ---2.8 and -4.4 diopters, respectively. Although the segm~nt cone angles varied, each segment had a thickness (t) of about 0.15 mm and was inserted at a depth (d) in the cornea of about 0.42 mm.
Based on the variables listed above, the following equation, which defines a m~ hinp cone angle for a given DCC (which is equal to 2 RCC) Ri and d, was derived.
Dcc (1) ~ = sin~l , where 2(Rj-d) ~, DCC~ Rj and d are as defined above.

The following table provides m~tc.hing cone angle values (~) in degrees rounded to 25 the nearest tenth of a degree for a segment implanted at a depth of 0.42 rnm and for an initial corneal radius of curvature (Rj) ranging from 7.6-7.9 mm (which is the tvpical range in the population) and center to center diameters (DCC) ranging from 5.0-8.0 mrn according to the above equation.

WO 97/28759 PCTfUS97tO1411 Dcc R; 5.0 5.5 6.0 6.5 7.0 7.5 8.0 7.6 20.2 22.5 24.7 26.4 24. 13 1 .5 33.7 - 7.7 20. 1 22.2 24.3 26.5 28.7 3 1 .0 33.3 7.8 19.8 21.9 24.0 26.1 28.3 30.5 32.8 7.9 19.5 21.6 23.6 25.8 27.9 30.1 32.3 The above calc~ tion~ are merely e~ennrl~y and not int~(lecl to lirnit the invent;on. For example, the implantation depth "d" may range from about 0.10-0.50 mm, even though a value of 0.42 mm is used throughout the above calculations for purposes of 5 example.
A mi~m~tching cone angle is one that does not equal the cone angle described in equation (1) for a given D~ (equal to 2RCC), R; and d. Thus, for example, given a DCC of 7.0 rnm, an Rj of 7.6 mm and a "d" of 0.42 mm, a mi~m~rhing cone angle would be any cone angle that is not equal to 24.1 degrees.
Another e~uation for describing a cone angle that is a matching cone angle is er~lled when accounting for segment thicknesses above about 0.15 mm, which provides sufficient thickness to flatten the cornea independent of cone angle. According to this refined equation:

Dcc (2) ~ = sin~l , where 2[(Rj-d)+~ ]

'\Rt = the expected radius of corneal curvature change induced by segment 20 thickness independent of cone angle for a given transverse, cross-sectional shape of any particular segment design. ~lt~ tively, ~R; can be described as the initial radius of - corneal curvature minus the final radius of corneal curvature as previously described above where ~Rt is deterrnined based only on the change induced by the segment thickness independent of cone angle for a given radial, transverse cross-sectional shape of any 25 segment.

WO g7/28759 PCT/US97/01411 Thus, when accounting for such thickne~es, a mi~m~tchtng cone angle is one that does not equal the cone angle described in equation (2) for a given DCC (equal to 2RCC), Ri, d and ~Rt.
The discussion of cone angle of segments has, thus far, been limited to segments5 having a constant cone angle across its length. I Iowever, segment~ having a cone angle which varies along the length of the se~m~nt or, in other words, a segment having multiple cone angles is also contemplated by the present invention. Referring now to Figs. 9-11, a se~rnent having more than one cone angle is shown. In this embodiment, segment 102"' is provided with multiple cone angles. This construction is particularly advantageous for 10 treating astiEm~ti~nl (or ~sti~m~ti~m concurrent with either myopia or hyperopia) where the corneal curvature varies in different m~rit1i~n~. In the embodiment shown in Fig. 9, the segment cone angle changes along the ci~ r~l~lllial direction thereof. Generallyspe~kin~, the segment has a first cil~ rGlGl~lial region having a first cone angle and at least one other region having a cone angle that differs from said first cone angle.
In the example illustrated in Fig. 9, the segmf~nt has three circumferential regions with distinct cone angles. Circumferential region 202 has a first cone angle ~1 as shown in Fig. 10. Circumferential region 202 is followed in the clockwise direction by a second circurnferential region 204 having a second cone angle ~2~ as shown in Pig. 11 that substantially differs from the first cone angle ~1. That is, the cone angle varies enough for treating ~tipm~fi~m (or astip~m~ti~m concurrent with either myopia or hyperopia) as discussed below. Ci~ -Çe~e.llial region 206 follows region 204 with a cone angle similar to that of region 202 in the clockwise direction.
Fig. 12 shows another embodiment of the present invention. Two segments 210 and 220 are shown positioned opposite each other such that they forrn a ring-shaped structure having two splits. In the example of Fig. 12, segments 210 and 220 have multiple cone angle values and arc angle and length values which are substantially similar to each other and to segment 102"' of Fig. 9. The cone angles of the respective segments 210 and 220, and of the resulting ring-shaped structure, changes along the circumferential direction thereof. In the example illustrated in Fig. 12, the structure has six circumferential regions with distinct cone angles. Segment 210 has a first circumferential region 212 which has a first cone angle ~1 as shown in Fig. 10. Circumferential region 212 is followed in the clockwise direction by a second circumferential region 214 having a WO g7/28759 PCT/US97/01411 second cone angle ~2, as shown in Fig. 11, that subst~nti~lly differs from the first cone angle ~l. Circumferential region 216 of se~men~ 210 follows region 214 with a cone angle similar to that of region 212 Circumferential region 222 of segment 220, which follows region 216 in the clockwise direction, has a cone angle similar to region 216. The cone S angle varies again in region 224, which has a cone angle similar to that of region 214 of segment 210. Finally, region 226 of segment 220 has a cone angle similar to that of regions 212, 216, and 222.
As discussed with respect to Figs. 9-11, the o~L~ values of the respective arc angles and cone angles for a particular segm~nt with a particular cross-sectional area shape is dependent upon the vision problem being treated, the radius of curvature of the segment and the flexural modulus of the segment. Typically, for treating ~tigm~ti~m with either myopic or hyperopic problems, two or more segment~ may be used. The two or more segment~ may have identical cone angles, thickness, and arc length, but may also differ from each other with respect to one or more of these parameters. Thus, although an intracorneal insert having a particular number of segment~ each having particular multiple cone angle and arc angle configurations has been shown, other configurations can be used.
~or example, any nurnber of segments may be used, each having various m~tc~lin~ or mi~m~ltching cone angle configuration and arc angles for treating an individual's particular problem.
As discussed above, an important aspect of the present invention is that the shape of the anterior corneal surface, and particularly the radius of ~ , may be adjusted by using segments having mi~m~t~ e~ cone angles. This aspect is generally illustrated in Figs. 13, 14, and 15 where the effect of m~t~ ing (Fig. 13) and mi~m~tchinp~ (Figs. 14 and 15) cone angles is compared. Each of these three Figures shows a cross-sectional view of a pair of opposing segments sirnilar to those described with respect to Fig. 12.Fig. 13 shows a pair of opposing segments 300 and 302 having cone angles which match the inner l~m~ell~r architecture. In Figs. 14 and 15, there are shown segment pairs having mi~m~t~ hed cone angles. In other words, their respective cone angles do not match the inner lamaellar architecture. The phantom lines shown in these figures correspond to the outer lines of the cornea section of Fig. 13 and thus provide a reference for the corneal configuration changes caused by the respective segment pairs with mi~miqtchirlg cone angles. Referring particularly to Fig 14, segments 304 and 306 are shown with cone angles greater than those shown in Fig. 6. The larger cone angle twists adjacent portions of the cornea outward and flattens the central region of the cornea between segments 304 and 306 as shown in the drawing. This particular configuration is helpful in treating myopia. In contrast, Fig. 15 shows a pair of ~egment~ 308 and 310 having cone angles less 5 than that shown in Fig. 13. This smaller cone angle effects a steepening of the corneal surface as shown in the drawing and is helpful in treating hyperopia.
Thus far in this description of the present invention, one or more segments having one or more mi~m~t- hed cone angles have been ~ cll~secl which are used to effect a change in the radius of curvature of the cornea. Another aspect of the invention is to 10 employ segment~, with or without mi.~m~tch~tl and/or multiple cone angles, which have varying cross-sections, or otherwise vary in thickn~s~ and width along their arcs, to effect the desired alteration of the radius of curvature, and in particular to correct for ~c1i~m~ti~m Referring now to Figs. l 6- l 7, an embodiment of the segments of the present invention are shown in which the individual segm~-nt.~ have at least one region in which the l 5 cross-section is thicker or the bulk of that region is more pronounced. Often these segment~ will have two or more regions at which the bulk is increased. By proper~1ignm~nt of the various regions of the segment with the areas of the eye that need correction, the proper radius of curvature may be achieved.
In Fig. 16, there is shown two segments 350 and 352 each having a region 354 of 20 added bulk or dimension shown to extend over a region of about 90c Of the respective segments. Although regions are shown to be substantially symmetrical, other embo-1iments in which more than one segment is used and in which the respective regions of enh~n~efl ~1imen~ion are in an asymmetric configuration are also collLe~ lated by the present invention. The regions of added dimension are critically tailored to correct the 25 ~stiFm~ti~m or asti~çrm~ti~m in combination with either myopia or hy~elol~ia found in a particular eye.
~ ig. l 7 illustrates a segme~t 380 in which the thickness of at least one portion of the segment is thicker 382 than another thinner portion 384 of the segment 380. The nurnber of thicker portions of the segment may be one or more depending upon the30 astigmatic aberration to be corrected.
In general, the thickness of the regions of added bulk may range from about 0. lmm to less than 0.5 m~n. This thickness range is suitable for segments, to treat CA 02216205 lss7-lo-os asti~m Itism alone or in conjunction with either myopia or hyperopia, which have arc angle ranges and corresponding constant and variable cone angle ranges discussed above.
Furthermore, the regions 354 subtend an arc of at least about 2~ measured from the center of an im~gin~ry ring having identical cross-sectional f1imencions and radius of 5 curvatllre as the segment. More typically the regions of larger ~limen~ion will subtend about :10~ to 90~ and more preferably about lQ~ to 60~. When mllltir)le sections of added ~limçn.sion are used, each section may be of the sizes listed above for the single arcs. The sum of all of the subtended arcs for the segment is preferably less than about 350~.
Also contemplated by the present invention is the use of hydratable and swellable 10 polyrners for m~kin~ these segents such that the ~limen~ions, and particularly the thicknes~es, of these segments can be adjusted in sifu after insertion into the cornea. Such aspects of the present invention are ~ cu~ecl in detailed below.
Particular values of the segment parameters ~ c~ ecl above are selected based upon the corneal curvature correction to be effected. ~e values of some of the individual 15 parameters may be dependent upon the other parameter values selected, such as the radius of ~ v~LLIle and Young's modulus of elasticity of the segment. Accordingly, suitable values for each parameter are generally defined within a range. The following discussion of acceptable value ranges for cone angle, thickness and arc angle is based upon segments having a radius of curvature of about 3.25 mm and comprised of polymeric m~t~ l having 20 a flexwral modulus of elasticity greater than about 3.5 kpsi.
Generally, values for a se~ment's cone angle, whether constant or variable across the segments length, are between about 0~ and 160~, preferably between about 0~ and 80~, and more preferably between about 0~ and 60~. In general, the value of a segment's arc angle is less than 360~, typically less than 340, more typically 320~, and most typically 25 less than 270~. Segment thickness, whether constant or varying across the length of the segment, ranges from about 0.1 mm to about 0.5 mm.
Many combinations of particular values within the above ranges are acceptable for correction vision problems. However, for purposes of correcting ~ti~m~ti~m where no myopic or hyperopic correction is needed, the combination of variables requires a more 30 specific range of values. Specifically, with segments having a constant cross-sectional area and a constant cone angle along their lengths, suitable arc angles are between about 10~
and 90~, preferably be~veen about 20~ and 60~, and more preferably between about 30~

CA 0221620~ 1997-10-09 and 50~. However, for treatment of pure astigmslti~m with segments having variable thickness and/or variable or multiple cone angles along their lengths, suitable arc angles are between about 90~ and 175~, preferably between about 100~ and 175~, and morepreferably between about 140~ and 165~. ~imilarly, for treatment of conditions other than 5 pure astigm~ti~m (such as myopia, hyperopia, or combinations of myopia with asti~m~ti~m~ or combinations of hyperopia with ~tigm~ti~m) suitable arc angles are between about 90~ and 175~, preferably between about 100~ and 175~, and more preferably between about 140~ and 165~, regardless of whether the segment has a varying or constant thickness or a varying or constant cone angle. It should be noted, that for treating 10 asti~m~ti~m in combination with either myopia or hy~lupia, a segment having certain other prescribed parameters (such as variable thickness or multiple cone angles) in addition to the above prescribed arc angles may also be used.
The materials used in the segment~ of the present invention preferably have a shape and sufficient strength such that the segment is not easily damaged by the forces put upon 15 it when it is inserted into the eye. A certain mil~i."l.,.. flexural modulus of elasticity is necessary for segment~ having mi~m~tt~hing cone angles in order to ,~;n~;lin themi~m~t~hed angle over time. Thus, with segment~ having a mi~m~tched cone angle, relatively stiff~ physiologically acceptable polymers having a high flexural modulus of elasticity are preferable. Materials having a high flexural modulus of elasticity are those 20 having moduli greater than about 3.5 kpsi.
Acceptable physiological polymers having a sufficiently high modulus of elasticity include polymethylmethacrylate (PMMA), TEFLON, polycarbonate, polysulfones, epoxies, or polyolefins such as polyethylene, polypropylene, polybutylene, and their mixtures and interpolymers. Many of these polymers are known in the art to be 25 ~plo~,liately used in hard contact lenses.
The polymeric m~t~n~l making up the segment may be a hybrid which includes more than one polymeric layer. The polymeric layers may be comprised of, for example, one high modulus and one low modulus polymer, or two high modulus polymers, or two low modulus polymers. Low modulus polymers have a Young's modulus of elasticity 30 below about 3.5 kpsi. This class of polymers include physiologically compatible elastomers and such crosslinked polymeric gels as polyhydroxyethylmethylacrylate(Poly-HEMA) or polyvinylpyrrolidone (PVP), polyethylene oxide, or polyacrylates, CA 02216205 lss7-lo-os wo 97/28759 PCTrU$97/014 polyacrylic acid and its derivatives, their copolymers and interpolymers, and the lilce as well as biologic polymers such as crosslinked dextran, cros~linked heparin, or hyaluronic acid.
As mentioned above, because a certain minimll7n amount of segment rigidity is necessary to m~in~in mi~m~tched cone angles over time, care should be taken to ensure that the overall rigidity of hybrid segments comprised of one or more layers of low modulus polymers is sufficient.
The segments of the present invention may also be hydratable. Partially hydratedor fully hydrated hydrophilic polymers are typically slippery and consequently may contribute to the ease with which the insert may be introduced into the inf~rl~m~ellar tunnel.
Suitable hydrophilic polymers include polydroxyethylmethacylate (pHEMA), N-substituted acryl~mi~le~, polyvinylpyrrolidone (PVP), polyacrylamide, polyglycerylmethacrylate, polyethyleneoxide, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, poly (N, N-dimethyl amino propyl-NI-acrylamide) and their copolymers and their combinations with lly~ l ilic and hydrophobic comonomers, crosslinks, and other modifiers. Thermoplastic hydrogels include hydropoly-acrylonitrile, polyvinyl alcohol derivatives, hydrophilic polyurethanes, styrene-PVP blocl{ copolymers and the like.
The intrastromal corneal segment may be lubricated with suitable ocular lubricants such as hyaluronic acid, methylethyl cellulose, dextran solutions, glycerine solutions, polys~cçh~ricles> or oligosaccharides upon its introduction to help with the insertion particularly if one wishes to insert intrastromal segments of hydrophilic polymers without prior hydration. ~f a hybrid segment having a hydrophilic polymeric covering or a segment comprising a hydrophilic polymer is inserted into the eye without prior hydration, subsequent to the insertion, the intrastromal segment will swell to its final size or thickness within the eye. This swelling often permits the inclusion of larger intrastromal segments than ~ould normally be accommodated within normal sized intrastromal channels.
Low modulus polymers used in this invention are often absorbent, particularly ifthey are hydratable, and may be infused with a drug or biologic agent which may be slowly released from the device after implantation of the intrastromal segment. For instance, the low modulus polymer may be loaded with a drug such as dexamethasone to reduce acute CA 0221620~ 1997-lO-09 infl~mm~tory response to implanting the device. This drug helps to prevent undesirable scarring or vascular ingrowth toward the intrastromal segment. Similarly, heparin, corticosteroids, antimitotics, antifibrotics, ~ntiinfl~mm~tories, anti-scar-forming, anti-adhesion, and ~nti~ngiogenesis factors (such as nicotine adenine dinucleotide (NAD+)~
may be included to reduce or prevent angiogenesis and infl~mmRtion. Clearly, there are a variety of other drugs suitable for inclusion in the illLId~L.vlllal segment. The choice will depend upon the use to which the drugs are put.
Each of Figs. 1 8A-C, 1 9A-C, 20A-C, and 21 A-C, shows respectively a front view("A" drawing) and a cross section ("B" drawing) and a side view ("C" drawing) of various narrow point intracorneal inserts made according to the invention. Although these drawings show narrow points on the inventive inserts, such points are not a critical aspect of the invention. The ends of the inserts may be tapered in both width and thickn~s~, in one or the other of those axes, or may be blunt. Other variations of the ends will be c~ ed below to the extent n~c~ ry to understand the invention. These inserts are"pre-formed" or "pre-shaped." By the use of these terms, it is meant that the insert has sufficient structural integrity to approxim~tt~ the shape of some portion of the intrastromal channel into which it is to be placed.
Figure 1 8A shows a front view of a pre-shaped intracorneal insert 400 having ends 402. The intracorneal insert tapers both in width and in thickness to narrow points 402.
Viewed in cross section in Figure 1 8B, the generally smooth convex front surface 404 and planar rear surface 406 may be seen. Figure 1 8C shows a side view of the segrnent or insert.
Figure 1 9A shows a front view of an intracorneal insert 500 having ends 502.
Again, the intracorneal insert tapers both in width and in thickness to narrow points 502.
Viewed in cross section in Figure 1 8B, the generally hexagonal shape may be seen. The sul~ces most adjacent the anterior surface of the eye and the side just opposite are generally the two longer of the sides. Those generally planar front surface 504 and planar rear surface 506 may be seen. Figure 1 9C shows a side view of the segment or insert.
Figure 20A shows a front view of an intracorneal insert 600 having ends 602. Theintracorneal insert tapers both in width and in thickness to narrow points 602. Figure 20B
shows the generally round cross section. The cross section may also be oval-shaped with the major axis of the oval either as the width or the thickness or neither. Figure 20C shows CA 02216205 lss7-lo-os a side view of the segment or insert which, because of the symmetry of the device, is the same as the top view.
- Figure 21A shows a front view of a hybrid intracorneal insert 700 having ends 702.
Again, the intr~eorn~l insert tapers both in width and in thic kness to narrow points 702.
5 Viewed in cross section in Figure l9B, the generally hexagonal shape may be seen. This set of Figures is to show the concept of a multilayered insert made up of polymers of dirfe.~ characteristics. In this example of a multilayered insert, the hybrid inkastromal segment has inner 702 and outer faces 704 of polymers having low moduli of elasticity.
Low rnodulus polymers are those having a Young's modulus of elasticity below about 3.5 kpsi, more preferably between 1 psi and 1 kpsi, and most preferably between 1 psi and 500 psi. They must be physiologically compatible with the eye. This class of polymers includes most polymeric materials used in soft contact lenses.
The inner portion or core 706 as shown in Figure 21B may be a physiologically compatible polymer having a high modulus of elasticity. As discussed above, highYoung's modulus of elasticity is considered to be greater in value than about 3.5 kpsi, preferably 5-10 kpsi, and most preferably 8-10 kpsi.
If hydratable polymers are chosen for the outside layers, the extent to which those outer layers swell upon hydration is dependent upon the type of polymer chosen and, when the polymer is hydratable, upon the amount of cross-linking found in the outer layers 702 and 706, and upon the thickness of the layer. Generally speaking, the more highly linked the hydratable polymer, the smaller the arnount of volume change upon hydration.Alternatively, a sl~st~nti~lly nonswellable polymer system may be formed of a hydrogel physically interpenetrated by another polymer which does not hydrate, e.g, polyHEMA, to limit its degree of swelling and water absorption.
The thickness of the outer layer depends in large function upon the intended use of the intrastromal segment. If the outer layer is used to provide a swellable outer layer which does not add significantly to the size of the intrastromal segment or is used functionally as a lubricant layer, the other layer may be quite thin -- even to the point of a layer of minimum coverage, perhaps as thin as a single molecular layer.

3~ Of course, the inner and outer layers need not be, respectively, low modulus and high rnodulus polymers but may instead be multiple layers of low modulus polymers CA 0221620~ 1997-10-09 WO 97/28759 PCTtUS97101411 including an outer hydrophilic polymer layer and an inner hydrophobic polymer; a variety of hydrophilic polymers; etc.
Additionally, the inventive device shown in Figs. 21A-C need not have a inner 704 and outer 702 layers over the entire i,lL,d~l,ulllal segment. For instance, to alleviate 5l~ti~m~ti~m, an intrastromal sçgment having a thicker portion and a subst~nti~lly thinner portion may be desired. An intrastromal segment having an inner core of a high modulus polymer and an outer covering of a swellable polymer might be chosen. The surgeon would remove a portion of the i,lLIdsl~ al segment's exterior coating or face prior to introducing the intrastromal segm~nt into the eye. Further, and as will be discussed below in greater detail, hydrophilic polymers are more easily infused with therapeutic and diagnostic materials than are the high modulus materials. In the variation just noted, the insert may then be used to deliver the infused therapeutic and diagnostic materials in a greatly delimited of treatment or diagnostic area.
Fig. 22A shows a front view of an wide end intracorneal insert 800 having ends 802. In this variation, thé insert tapers only in thickness to form a spade-shaped end 802.
Viewed in cross section in Fig. 22B, the generic shape may be seen. Fig. 22C shows the same shape but nearer to the end of the device. This set of figures is to show the concept of a single-tapered end.
Fig. 23A is a front quarter view of a variation of the intrastromal segment 900 made of a low modulus polymer system hydratable outer coating 902. Fig. 23C shows the inner cavity 904. This intrastromal eegment may be inserted into the inl~ o,l,al space created by the ~ sectQr as a covering on a tool similar to the ~ ector which created the intracorneal channel. Once in position the insertion tool is rotated out of the intrastromal segment leaving the shell within the stroma.
Fig. 23C shows the inner cavity 904 which may be filled with a biologic, a drug or other li~uid, or biologically active eye treatment m~tt ri~ These devices may be tied or pinched or crimped or otherwise connected at their point of insertion by known techniques.
The shell 906 may be injected with a settable soft polymer core, allowed to expand to a desired thickness, and set. Polymeric gels which do not polymerize in situ are plerelled. Suitable injectable polymers are well known but include polyHEMA hydrogel, cross-linked collagen, cross-linked hyaluronic acid, siloxane gels, and organic-siloxane gels such as cross-linked methyl vinyl siloxane gels.

CA 02216205 1997-lO-09 Fig. 24 shows a variation of the invention in which an assemblage of the inventive intraskomal segments 950 are formed into a polymeric ring or, at least, into an assemb~age ~ which totals no more than 360~ of corneal circumference when assembled into the intracorneal space. The two s~gment~ 950 depicted in Fig. 24 may be of any of the 5 individual variations shown in the Figures above and need not be connected in any way.
Fig. 25 shows a similar assemblage in which the intracorneal segments 952 are held together using open holes 954 and a clip 956 which may be a simple wire or other suitable joining device. An assemblage such as is seen in Fig. 25 may be advantageously inserted from a single central opening, as will be described below.
Fig. 26 shows a variation, an assemblage of segments, in which the sections 960 are strung together on a fil~merlt 962. The se~mPn~ 960 have an open pathway along their length (see cutaway) which permits such stringing Figs. 27A and B show a variation of the inventive intracorneal inserts in which two or more inserts overlap to form an assemblage. The top view shown in Fig. 27A
15 depicts the assemblage as found in the eye. The assemblage need not be formed of segment~ of the same or similar width or thickness or m~tP.ri~l of construction nor need the assemblage be limited to the semicircle shown in Fig. 27A. Although a front-to-back assemblage is depicted in Fig. 27B, the junction between the sections (964 and 966) may be of any other design which allows contact between the adjoining sections and remains 20 relatively immobile after the placement in the cornea. For instance, the design shown in Figures 27A and 27B involves the use of a smooth interface. The intrastromal channel normally exerts a force against the assemblage and will m~int~in the se~m~nt~ in the depicted relational position within the eye.
Although particular embo-liment~ of segment assemblages have been illustrated in25 the Figures, other assemblages are acceptable. The segments may be of similar or quite different configurations depending upon the indication to be remedied. For exarnple, rather than overlapping or being positioned end-to-end, the segments may be stacked one on top of the other to forrn a thicker insert. Additionally, the segments may be inserted in ~ separately produced intrastromal channels which may, or may not, be in communication 30 within the cornea. Such individual insertion will be discussed in more detail below.
The present invention includes methods for inserting the above-described inventive segments into the cornea of the eye in which partial arc se~ments are introduced into CA 0221620~ I gg7 - lO - 09 W097/28759 PCTrUS97/01411 separate sections of the corneal circumference outside of the optical zone of that cornea. In particular Figs. 28A-~ depict a method of inserting more than one segment through more than one entry slit within the cornea. Figs. 29A-F, on the other hand, illustrate a method of inserting one or more segments through only one entry slit with the cornea. Specifics of 5 surgical devices which may be used to make the initial corneal slits and intrastromal channels, e.g, dissectors and supporting devices, may be found in PCT Publication No.
PCT/US93/032~4, PCT PublicationNo. W09320763 entitled "Corneal Vacuum ~entf~rin~Guide and Dissector," and PCT Publication No. W009403 129 entitled "Hybrid Intrastromal Corneal Ring" the entirety of which are incorporated by reference.
Turning now to a discussion of one of the methods, Fig. 28A shows a frontal viewof an iris 800 and a pupil 802. As was described above, the cornea is clear and is not visible in these drawings. First, an entry slit 804 is made radially into the cornea. A
dissector blade (not shown) is introduced into the entry slit 804 and turned in the direction of the arrow 806 to form a partial intrastromal rh~nnel of a desired length. A second entry slit 808 may then be made in the cornea and a second intrastromal ch~nnel be made in the direction of the arrow 810, as shown in Fig. 28B. I~e first and second ch~nnel~ have been shown to be forrned by turning the .li ~sectc r blade in counter-cloc~wise and clockwise directions, respectively, for purposes of describing the invention. ~Itçrn~tively, the entry slits may be made at other radial locations around the cornea, with channels formed in respectively opposite directions form those described. Additionally, the channels may be formed in the same direction, for example, where the entry slits are 180~ apart.Fig. 28C shows the introduction of a first inventive segment 812 into the first entry slit 808. Fig. 28D shows first segment 804 in its ffinal resting position and the introduction of a second segment 814 into the second entry slit 808. Finally, Fig. 28E shows both first segment 804 and second segment 814 in their final position within the cornea. As finally positioned, neither segments 804 and 814 are in contact with the two initial incisions so as to facilitate healing of the incisions. This method demonstrates the flexibility of the procedure in that e;ther clockwise or counter-clockwise insertion is ~ p-iate and the intrastromal channel need not be a complete circle about the cornea.
Figs. 29A-F schematically portray a method for the insertion of the segments described above in which partial arc segments are introduced into separate sections of the CA 02216205 1997-lO-09 corneal circumference outside of the optical zone area of that cornea through a single entry slit.
Fig. 29A shows the making of an initial entry slit 840 radially into the cornea. A
dissector blade (not shown~ is introduced into the entry slit 840 and turned in a counter-5 clockwise direction as indicated by arrow 842 to form a partial intrastromal channel of adesired length or angle, typically from about 0~ to 350~. In the illustrated method, the channels are shown to have about a 180~ arc. As is shown in Fig. 29B, a second intrasbromal channel is made by means of rotating a dissector blade (not shown) in the clock~7vise from about 0~ to 350~ in a direction, as indicated by arrow 844, from the same 10 initial entry slit 842. Alternatively, the procedure may begin with forming a channel in the clockwise direction, however, for purposes of this discussion, a procedure that begins with forming a channel in t,he counter-clockwise direction is described. With either procedure, the rh:~nnel.~ are formed in opposite directions. The two r.h~nnel~ may meet to form one 360~ channel, overlap each other, or preferably forrn one channel which is less than 360~.
Fig. 29C shows the introduction of the first segment 846 into the entry slit 842.
Fig. 29D shows the first segment 84~ in its final resting position. Fig. 29E shows the introduction of the second segm~t 848 into the entry slit 840. Finally Fig. 29F shows both first segment 846 and second segment 848 in their final position within the cornea.
Again, both segments are positioned away from the incision point to facilitate he~lin~ of 20 the incision.
Alternatively, the present invention cc-nt~mrlates forming one channel having anarc angle of 350~, for example, into which two or more segment~ may be introduced and positioned within the channel as desired.
Because of the nature of certain of the segments of the present invention, a large 25 measure of adjustability is available in the process of inserting the segment~ For instance, it has been found that when using various inserts (particularly with ocular lubricants) that the inserts may be "pushed" nearly 1 8û~ or more around a previously created intrastromal channel for insertion and then easily removed, if so desired. This observation means that the following procedure may be used. The eye of a person having myopia and/or 30 astipnn~ti~m may be measured to determine the proper amount of correction needed. From this information, the size and placement of one or more segments may then be chosen.
After inse~ion in the appropriate channe}s, the vision of the eyc might again be measured.

CA 022l6205 l997-lO-09 WO 971~8759 PCT/US97/01411 If insufficient correction of an indication is found, the insert may need to be rotated within the channel or be withdrawn ~partially or completely) and trimmed prior to complete re-insertion. Alternately, it may be n~c.o~s~ry to replace the segment with another segment having a di~erelll cone angle, radius of curvature, arc angle, or thickness in order to more 5 accurately treat the particular corneal problem. Such adjustability is not normally available when dealing with prior art inserts such as gel-based rings or with surgical techniques based on radial keratotomy.
The following two examples, based on clinical procedures, are int.onrlecl to further illustrate the method discussed with respect to Figs. 29A-F but are not int~n~led to limit the 10 invention in any way.

The eye at issue required correction of myopia. It was determined that the amount of correction required was between -2.0 to -2.5 diopters. Based on the amount ofcorrection to be achieved, it was ~ t~rrnined that t~,vo segments, each having a thickness of 0.3 mrn, an arc angle of 150~, and a constant cone angle of 34~, should be symmetrically positioned about the vertical axis. The insertion procedure involved making an entry slit, similar to that shown in Fig. 29A, and forming a counter-clockwise channel having an arc of 210~. Then, from the same entry slit, a clockwise channel also having an arc of 210~
was formed in the opposite direction, similar to that shown in Fig. 29B. The two segment were then inserted into their respective channels and positioned syrnmetrically opposite each, similar to that shown in Fig. 29F. Measurements showed that the desired power correction of-2.5 diopters was achieved.

The eye at issue in this exarnple was astigmatic, requiring -3.0 diopters of correction. Here, two segrnents, each having a thickness of 0.40 rnm, a cone angle of 34~, and an arc angles of 45~. The sarne insertion procedure was used to position the segments symmetrically opposite each other about the vertical axis, sim;iar to the arrangement shown in Fig. 29F. Measurements were taken showing a correction of only -5.0 diopters, -2.0 diopters in excess of the desired correction. The segments were then rotated out of the channels and replaced with segments having the same arc and cone angles but having a thickness of 3.0 mm. Meas~elllents then showed that the increase in thickness of the segments had achieved the desired -3.0 diopter correction.

WO 97/287S9 PCTtUS97tO1411 The above is a detailed description of particular embodiment of the invention. It is recognized that departures from the disclosed embo~im~nt~ may be made within the scope of the invention and that obvious modifications will occur to a person skilled in the art.
The full scope of the invention is set out in the claims that follow their equivalents.
5 Accordingly, the claims and specification should not be construed to unduly narrow the full scope of protection to which the invention is entitled.

Claims (16)

Claims:

1. An intrastromal corneal insert comprising a preformed, physiologically compatible, polymeric arcuate segment having an are angle less than 360° and in which at least one of the following characteristics varies over the are angle of the segment: cone angle, width, thickness, and modulus of elasticity.

2. The insert of claim 1 wherein the cone angle varies in the range of 0° and 180°.

3. The insert of claim 2 wherein the cone angle varies in the range of 0° and 60°.

4. The insert of claim 1 wherein the cone angle varies continuously.

5. The insert of claim 1 wherein the cone angle varies step wise.

6. The insert of claim 1 wherein the thickness varies in the range of about 0.1 mm and about 0.5 mm.

7. The insert of claim 1 wherein said segment has an are angle suitable for treating pure astigmatism.

8. An intrastromal corneal insert for implantation in a cornea having an anterior surface, said insert comprising an arc-shaped segment having a radius of curvature, a cone angle, an outer surface, a major axis for each radial, transverse cross-section thereof ,and a major axis line for each said cross-section, each major axis linedefined as the line that extends along a respective major axis and is bounded bysaid outer surface of said are-shaped segment, said cone angle being one that if an imaginary ring, having the same radius of curvature, major axes, and major axes lines as said are-shaped segment, were superimposed at an insertion site in saidcornea prior to actual insertion of said are-shaped segment, the major axis of substantially any radial, transverse cross-section of said imaginary ring would not be parallel to a line in the same plane as that major axis and tangent to the anterior surface of the cornea at the point where a line, that bisects the major axis line and is perpendicular thereto, intersects said anterior surface of the cornea.

9. The arc- shaped segment of claim 8 wherein said cone angle varies along the circumferential direction of said segment.

10. The arc-shaped segment of claim 9 wherein said segment has a first circumferential region having a first cone angle and at least one other region having a cone angle that differs from said first cone angle.

11. The arc-shaped segment of claim 8 having multiple cone angles.

12. The arc-shaped segment of claim 11 wherein said cone angle is selected to maintain said anterior surface in substantially an aspheric shape.

13. A surgical system or kit for use in correcting refractive characteristics of an eye comprising at least two intrastromal corneal inserts that are preformed, physiologically compatible, polymeric arcuate segments having an arc angle less then 360° which differ from each other in at least one of the following characteristics: cone angle, radius of curvature, width, thickness, and modulus of clasticity.

14. The system or kit of claim 13 wherein the inserts differ in cone angle and their cone angles are in the range of 0° and 180°.

15. The system or kit of claim 14 wherein the inserts differ in thickness and their thickness are in the range of about 0.1 and 0.5 mm.

16. The system or kit of any of claims 13-15 wherein the inserts have different are angles.