Intraocular lens implant

Abstract

The invention relates to an intraocular lens implant (12) for placement into the intracapsular space (3) of the lens capsule (13) of an eye and compositions, kits and methods relating to the lens implant (12). The lens implant (12) is designed to be placed into the posterior portion (3b) of the intracapsular space (3) after removal of the natural lens body (2) and has a convex posterior surface. The lens implant (12) is formed of one piece and made of a suitable transparent non-structural cellular material. This leaves the anterior portion (3a) of the intracapsular space (3) implant (12) free, the size of which is set to include at most 40% of the volume of the natural lens body.

Description

Technical Field

[0001] This invention relates to the fields of human and veterinary medicine, particularly ophthalmic surgery, and to intraocular lens implants for placement into the lens capsule. The invention also relates to compositions, kits, and methods related to lens implants. Background Technology

[0002] Intraocular lens implants for inserting the lens capsule are known in the art. Removal of the natural lens and replacement with an artificial intraocular lens is one of the most frequently performed surgical procedures worldwide, primarily for the treatment of cataracts. This procedure is also increasingly envisioned for treating other lens defects, such as age-related presbyopia. Typically, to minimize the risk of infection during surgery, care is taken to keep the opening to the eye and lens capsule as small as possible through which the natural lens body is removed and the artificial lens implant is inserted.

[0003] Therefore, various commercially available lens implants are suitable for insertion into the capsular bag through small incisions due to their small size and / or being made of flexible artificial materials such as silicone and acrylic materials. Typically, such small lens implants include an optical zone and one or more haptic elements for securing the implant to the capsular bag. Some adjustable lens implants available in the art attach a lens implant with haptic elements to the capsular bag, allowing it to adjust between myopia and hyperopia in response to the contraction and relaxation of the small band organs of the eye. However, the small size of such implants and the high refractive index of these flexible materials have led to an increased rate of post-cataract surgery photopsia, where light reflections on the retina interfere with vision, particularly at night. Another common complication of intraocular implants is the formation of secondary cataracts.

[0004] In another method described in EP1251801, a full-size lens implant is provided, the size of which approximately corresponds to the physiological size of the lens body. It comprises two components, both made of artificially manufactured materials, for replacing the lens body juxtaposed with the anterior and posterior medial surfaces of the capsular bag during implantation. The posterior portion of this two-piece implant is made of a solid material, preferably a flexible material, to facilitate its placement within the capsular bag. The anterior portion of this two-piece implant is artificially manufactured, for example, of a synthetic material or of a material based on isolated natural formulations, and includes, for example, polysiloxanes, hydrogels, or collagen compounds, which are preferably introduced into the capsular bag in a liquid state until the capsular bag is substantially filled, and then solidified in situ. The resulting two-piece intraocular lens implant thus generates intracapsular pressure similar to that of a natural lens body. The material (particularly the material of the anterior portion) is selected to have elastic properties similar to those of natural lens materials. Advantageously, this full-size intraocular lens is thus designed to interact with the eye's natural accommodation system, namely, with the zonula and ciliary muscle, just as the natural lens does. Contraction of the ciliary muscle causes the zonula to relax, resulting in a more rounded shape at the front of the two-piece implant. Therefore, as in the natural lens, the increased curvature of the implant surface provides accommodation for myopia. Furthermore, it overcomes some of the disadvantages of smaller implants mentioned above.

[0005] However, this two-piece full-size lens implant still has the same drawbacks as other types of adjustable lens implants: it has been found that the lens capsule loses its elasticity about 10 years after implantation of the artificial implant, accompanied by a loss of the ability to adjust for myopia. Summary of the Invention

[0006] Therefore, a general object of the present invention is to provide an improved intraocular lens implant, particularly in combination with a capsular filling composition, to overcome the disadvantages of existing intraocular lens implants.

[0007] In a first aspect, the present invention provides an intraocular lens implant for placement in the posterior portion of the intraocular lens space after removal of the natural lens body from the lens capsule of the eye. The lens implant is formed from a single component and is made of a suitable non-cellular structural transparent material. The lens implant does not enter the anterior portion of the intraocular space; that is, the anterior portion of the intraocular space remains free of non-cellular structural material or components thereof. The lens implant has no other portions formed of non-cellular structural material or components thereof. The size of the lens implant is configured to include at most 40% of the volume of the natural lens body. The lens implant has a convex posterior surface with a curvature shaped to conform to the curvature of the posteromedial surface of the capsule.

[0008] The terms natural lens or natural lens body refer to the actual lens or lens body removed through surgical procedures, or they can refer to the average size of the physiological lens or lens body representing a patient group such as adult patients. The term lens body refers to the portion of the lens that includes the lens fibers.

[0009] A transparent shell called the lens capsule (or simply the capsule) surrounds the lens body. Removing the lens body, including the lens fibers, from the capsule results in the capsule being essentially empty. This empty capsule contains virtually no lens fibers, but it still includes some or most of the lens epithelial cells lining its inner surface, particularly the anterior inner surface and the inner surface within the equatorial region along the capsule's equatorial circumference. Advantageously, a mild surgical procedure can be used that leaves most of the lens epithelial cells unaffected (see below).

[0010] The lens implant according to the invention is made of a suitable transparent acellular structural material. The transparency can be selected according to the therapeutic purpose of the lens implant and may include partially transparent materials. The term "acellular structural material" refers to a structural material suitable for replacing removed lens fibers, which does not include lens fibroblasts or other biological cells. Acellular structural materials are particularly flexible materials, including manufactured inorganic or organic, artificial or natural structural materials, such as, in particular, polymeric materials, such as polysiloxanes, hydrogels, or collagen. They are particularly selected from silicones, hydrophobic acrylic materials, hydrophilic acrylic materials, hydrogels, or collagen polymers. The term "subunit of acellular structural material" refers to a component of the structural material, such as a monomer, dimer, or oligomer of a polymer or polymer blend.

[0011] The lens implant according to the invention is formed of a single component that replaces up to 40% of the natural lens body; that is, the lens implant fills only up to 40% of the volume of a previously emptied capsular bag. In some embodiments, the material composition of the single-piece implant is homogeneous. In other embodiments, the material composition may vary in different regions of the lens implant. For example, it may differ in the central region around the visual axis from that in the equatorial region along the equatorial circumference. Because the lens implant is placed in the posterior part of the capsular bag, it keeps the anterior part of the capsular bag free of acellular material. The lens implant has no other components. After the lens implant is implanted, the remaining volume of the lens body will be reconstructed through the growth of cellular lens fibers.

[0012] Therefore, the lens implant is an intracapsular implant, wherein the implant is made by comprising a component of a transparent structural material that constitutes up to 40% of the volume of the removed natural lens. This monolithic lens implant is the sole deposit of non-cellular structural material within the capsular bag. The lens implant is shaped to replace only the posterior portion of the lens body and allows the anterior portion of the lens body to regenerate via lens fibroblasts.

[0013] The term "curvature of the posterior surface" (or simply posterior curvature) refers to the curvature of the posterior surface of the lens or lens implant, either juxtaposed with the inner posterior surface of the lens capsule. Clearly, these posterior surfaces are defined by the radii of substantially identical or concentric circular bodies. Specifically, the term "posterior curvature" refers to the posterior curvature of the lens and lens capsule in the relaxed state of the eye's ciliary muscle, i.e., in a state where the lens is adapted for hyperopia. However, it is noteworthy that the posterior curvature of the natural lens does not change much during accommodation, certainly not as much as the anterior curvature of the natural lens.

[0014] Furthermore, the natural curvature of the posterior surface of the lens and capsule is very close to that of a sphere. The average posterior radius of curvature of a physiological lens is in the range of about 5.5 mm to 6 mm. Therefore, the term "curvature of the posterior surface shaped to fit the capsule" refers to a substantially spherical posterior surface with a radius of curvature ranging from about 5.5 mm to 6 mm ± 25%, particularly ± 20%, 15%, 10%, or 5%. Thus, advantageously, the posterior surface of the lens implant, juxtaposed with the inner posterior surface of the empty capsule, does not necessarily fit without any gaps. The inventors have observed that such gaps between the posterior surface of the implant and the inner posterior surface of the capsule are filled by the remaining lens epithelial cells after implantation. Because in response to the reduced intracapsular pressure, these epithelial cells proliferate, grow, and differentiate according to their physiological pathways to form one, several, or perhaps multiple layers of clear epithelium and / or lens fibroblasts until physiological intracapsular pressure is reached. The observed thickness of newly formed tissue filling the gap ranged from 1 μm to 1 mm, typically reaching 100 μm or even several hundred μm, such as 200, 300, or 400 μm. This type of controlled tissue growth was only observed after implantation of a suitable implant, provided that the intracapsular pressure could still be reduced postoperatively, but preferably by less than two-fold compared to physiological intracapsular pressure. Conversely, if there is essentially no intracapsular pressure postoperatively, the remaining lens epithelial cells often participate in abnormal cell growth, leading to, for example, the formation of fibrous and bead-like structures and secondary cataracts (posterior capsular opacification).

[0015] In some embodiments, the maximum length of the radius of curvature of the posterior surface of the lens implant, which is juxtaposed with the inner posterior surface of the capsule, is greater than the length of the posterior radius of curvature of the natural lens body. The flexibility and elasticity of the capsule are capable of compensating for length increases of up to 25% compared to the length corresponding to the posterior radius of curvature of the natural lens, particularly up to 20%, 15%, 10%, or 5%.

[0016] In some embodiments, the posterior radius of curvature can be adjusted based on measurements of the natural lens body, such as those obtained by optical coherence tomography, prior to removal of the natural lens body. The posterior surface of the lens implant can be shaped to fit the measured surface of the removed lens body within tolerances, for example, up to 10 μm or up to 100 μm, 300 μm or 1 mm, or particularly within tolerances of about 100 μm ± 25 μm or 50 μm.

[0017] In a second aspect, the present invention relates to a capsular filling composition for use in intraocular surgery to fill the intracapsular space after removal of the natural lens body from the lens capsule of the eye and the introduction of a lens implant made of a suitable transparent noncellular structural material as described above. The lens implant, placed in the posterior portion of the intracapsular space, only partially replaces the volume of the natural lens body, up to a maximum of 40%. The volume of the filling composition introduced into the capsular is adjusted such that, together with the volume of the implant, it provides a filling of the capsular up to a volume that substantially reconstructs the volume of the removed natural lens body or a lens body of a suitable average size. The capsular filling composition is an aqueous composition and does not contain a noncellular structural material that itself serves as a structural replacement for the lens fibers of the natural lens body (2). The filling composition also does not include subunits of such material, particularly not subunits that can be used to form a polymer as a replacement for the natural lens fibers, for example by in vivo curing, as described in EP1251801.

[0018] However, the filling composition may include living cells for the regeneration and replacement of lens fibers that are originally present in the natural lens body. Alternatively or additionally, it may include biochemical components, particularly those described below that promote the regeneration of lens fibers from living cells, such as components that stimulate the proliferation and / or differentiation of living cells (especially lens epithelial cells).

[0019] Therefore, compared to conventional implants, the implants and filling compositions according to the invention preserve the anterior portion of the intracapsular space (particularly the anterior inner surface of the lens capsule with lens epithelial cells) from contact with noncellular materials and artificially manufactured structural components. This is important because the lens epithelial cells lining the anterior inner surface of the capsule secrete the basement membrane that constitutes the anterior lens capsule throughout lifespan. This maintains the flexibility of the anterior capsule for a long time. In fact, in individuals without lens implants, the lens capsule typically remains flexible up to around 80 years of age, whereas, conversely, after the implantation of conventional lens implants, the flexibility of the capsule often deteriorates to the point of impairing or disrupting accommodative ability approximately 10 years later.

[0020] Therefore, advantageously, the implant according to the invention, the capsule-filling composition according to the invention, and the kit comprising both thereof keep the anterior portion of the intracapsular space free of introduced intraocular lens implant material and non-cellular structural components that may interfere with the generation of lens epithelial cells in the basement membrane, thereby impairing the flexibility and accommodation of the capsule.

[0021] Furthermore, this filling composition advantageously provides a replacement for the volume required to establish intracapsular pressure, which substantially corresponds to the physiological intracapsular pressure prior to removal of the natural lens body. The filling composition, as a physiologically aqueous composition (e.g., physiological saline, optionally including other suitable components known in the art), allows or promotes the biological generation of lens fibers by endogenous lens epithelial cells retained on the inner surface of the capsule and / or by cells (particularly lens epithelial cells) introduced into or included in the filling composition along with the filling composition. Lin et al. (Nature, 531 (Page 323, 2016), Lovicu et al. (Exp Eye Res, 142 (Page 92, 2016) and recent work by others have demonstrated that lens epithelial cells can proliferate and differentiate into lens fibroblasts both in vitro and in vivo, demonstrating their ability to reconstruct the transparent lens body or a portion thereof. Furthermore, the filling composition can advantageously facilitate the implant's retention in the posterior portion of the intracapsular space.

[0022] During the initial period following surgery, as the lens fibers regenerate and gradually replace the natural lens body until it is no longer replaced by the implant, the accommodative ability of the treated eye gradually recovers over time. Advantageously, regardless of this regenerative state, a degree of distance vision can be achieved within hours after surgery due to the refractive power of the lens implant placed in the posterior part of the capsule.

[0023] In a third aspect of the invention, the lens implant described above and the capsule-filling composition described above are combined in a kit. The capsule-filling composition of this kit advantageously provides volume filling of the intracapsular space and promotes cellular lens fiber growth after removal of the natural lens body, while ensuring that the anterior portion of the intracapsular space is free of acellular material. This kit overcomes the disadvantages of prior art implants as described above. In particular, the physiological cellular replacement of the natural lens in the anterior capsular space provides the necessary sustained elasticity of the anterior capsular region.

[0024] Another advantage of the lens implant and filling composition according to the invention, as described above, is that it reduces the rate of posterior capsule opacification (secondary cataract) caused by the uncontrolled growth of cells remaining in the capsule. However, in cases where posterior capsule opacification does occur, juxtaposing the implant according to the invention with the inner posterior surface of the lens capsule allows for particularly effective treatment: the thickened and opaque area of ​​the posterior capsule can be completely removed by laser surgery (e.g., by posterior capsulotomy), using, for example, a YAG or femtosecond laser across the entire thickness of the posterior capsule without creating a hole in the shell surrounding the intracapsular space. Thus, the implant enables complete removal of the opaque area of ​​the capsule in a wider range of situations.

[0025] Another aspect of the invention relates to a method for providing a personalized intraocular lens implant or kit as described above for replacing the natural lens body. In some embodiments, the method includes step (a): providing measurements of eye size and / or optical power, and / or including measuring eye size and / or optical power. These results or measurements particularly relate, for example, the optical power of the cornea or natural lens, the size of the cornea or lens, the length of the eye along the visual axis, or the curvature of the posterior surface of the lens or lens capsule. Furthermore, the method for providing a personalized kit or implant includes step (b) as described above: selecting an implant, which step (b) adjusts based on the results provided or measured in step (a).

[0026] Another aspect of the invention relates to a method of medical treatment for a patient, the method comprising: surgically removing a natural lens body and replacing the natural lens body with an implant as described above and a capsule-filling composition as described above, the method being particularly useful for treating cataracts or presbyopia. Attached Figure Description

[0027] The invention will be better understood when taken in conjunction with the following detailed description, and objects other than those set forth above will become apparent. This specification refers to the accompanying drawings, in which: Figure 1 A cross-sectional view of a healthy human eye is shown, schematically depicting portions relevant to the context of this invention.

[0028] Figure 2 A schematic cross-sectional view of a human eye is shown after using an exemplary embodiment of the kit, which includes an exemplary embodiment of an intraocular lens implant and an exemplary embodiment of a capsular filling composition for introducing an intracapsular space after the natural lens body has been removed from the lens capsule. Detailed Implementation

[0029] exist Figure 1 The cross-section of the eye schematically shows the portion of the eye most relevant to the context of the invention, having a lens 1 and an equatorial diameter 5 between the two equatorial poles 6 of the lens 1, which divides the lens 1 into anterior and posterior portions. The term "anterior" refers to the side facing the cornea; the term "posterior" refers to the side facing the retina of the eye. The lens 1 includes a lens body 2, which is correspondingly divided into anterior portion 2a and posterior portion 2b along the equatorial diameter 5.

[0030] The lens body 2 is essentially composed of transparent lens fibers. The lens body 2 is surrounded by a capsule 13 having an anterior inner surface 13a and a posterior inner surface 13b. After the lens body 2 is removed, the essentially empty capsule (or empty capsular bag) forms an intracapsular space 3, which is divided into anterior portion 3a and posterior portion 3b along an equatorial diameter 5. The equatorial diameter 5 is the maximum diameter of either the lens 2, the capsule 13, or the intracapsular space 3, and is oriented substantially perpendicular to the visual axis.

[0031] The capsule 13 is composed of an extracellular basement membrane comprising type IV collagen fibers and sulfated glycosaminoglycans. The capsule is elastic due to the lamellar arrangement of the collagen fibers. The capsule 13 is secreted anteriorly by lens epithelial cells 4 and posteriorly by extending lens fibroblasts. Lens epithelial cells (LECs) 4 line the anterior inner surface 13a of the lens capsule 13, as magnified in Illustration A. LECs 4 have also been observed to line the inner capsule surface in an equatorial region extending into the posterior portion of the capsule. LECs 4 not only secrete the anterior portion of the lens capsule 13, but they also differentiate into extending lens fibroblasts in the equatorial region along the equatorial circumference of the lens 1. Furthermore, LECs are capable of proliferating and differentiating into lens fibroblasts not only in vivo but also in vitro, and they are capable of reconstructing the transparent lens body 2 or a portion thereof.

[0032] In cataract surgery, minimally invasive surgical techniques have been developed for removing defective lenses. In a common approach known as capsulorhexis, an incision is made in the capsule 13 (particularly in the anterior part of the capsule 13) to create a circular opening that allows the lens body 2 to be removed. In a commonly used procedure called phacoemulsification, the defective lens body 2 is emulsified by ultrasound and then aspirated. (See Zhou et al., Invest Ophthamol Vis Sci. 2016;) 57 The surgical procedure described (page 6615, see also Appendix 2) results in the capsular bag surrounding the intracapsular space 3 being substantially empty, while the natural lens body 2 has been removed from the anterior 3a and posterior 3b. Advantageously, using this minimally invasive surgery, the liner of the LEC 4 on the anterior intracapsular surface 13a and most of the lens capsule 13 remain unaffected. It has been shown that this allows for spontaneous regeneration of clear lens tissue (see, for example, Lin et al., 2016, Extended Data, cited above). Figure 1 Or Zhou et al., InvestOpthalmol Vis Sci. 2016, 57 (See page 6615, Appendix 2). In the medical treatment method according to the invention, which includes surgical removal of the natural lens body, particular attention is paid to incising into the capsular bag in the peripheral region of the lens capsule remote from the visual axis 11. Furthermore, care is taken to keep the incision size small, particularly keeping the maximum diameter of the incision hole less than 3 mm, especially less than 2.5 mm, 2 mm, 1.5 mm, or 1 mm. After the implant is introduced, the incision is closed, for example, by fibrin sealant or another bioadhesive. Alternative options for closing the incision include, for example, laser tissue welding, introducing a plug formed by a rotatable sheet closure, or introducing a plug formed by a small amount of curable artificial material (wherein the artificial material used is no more than the artificial material required to form the plug for closing the incision). Optionally, in some embodiments, a kit component for closing the incision into the capsular bag may be included.

[0033] Figure 1 A visual axis 11 perpendicular to the equatorial diameter 5 is also shown, which horizontally passes through the cornea 10, iris 9, and lens 1. Figure 1 In the diagram, the eye is depicted as being in a state of adaptation to farsightedness, as schematically illustrated by small band 7, as shown below. Figure 1 As shown, the small band 7 is circumferentially attached to the lens 1 at the two equatorial poles 6 along the equator. The small band 7 is shown in a stretched state, thereby flattening the lens 1. When the circular ciliary muscle 8 contracts, it relaxes the small band 7, which in turn allows the lens 1 to take on a more rounded shape, resulting in higher refractive power and thus adjusting the eye to myopia.

[0034] The radius of curvature of the posterior surface of the lens in the adult eye ranges from approximately 4.5 to 7.5 mm, while the average posterior radius of curvature is approximately 5.5 to 6 mm. The equatorial diameter of the lens in the adult eye ranges from approximately 9 to 11 mm. The volume of the lens in the adult eye, measured in vitro, ranges from approximately 180 μl to 280 μl (Rosen et al., Vision Research 2006). 46 (1002). The volume of the lens 1 in an adult eye basically corresponds to the volume of the lens body 2 and the volume of the intracapsular space.

[0035] Figure 2 An exemplary embodiment of an intraocular lens implant 12 placed in the posterior portion 3b of the intracapsular space 3 is shown. It is evident from this exemplary embodiment that the lens implant 12, made of a suitable transparent material, does not enter the anterior portion 3a of the intracapsular space 3. The volume of the lens implant 12 is less than 40% of the volume of the natural lens body 2; in the exemplary embodiment, it may be less than 20% or 10% of the volume of the natural lens.

[0036] In some embodiments, the size of the lens implant 12 is set to include up to 35%, 30%, 25%, 20%, 15%, 10%, 5%, or 2% of the volume of the natural lens body 2. Specifically, the size of the lens implant 12 is set to include a volume of up to 120 μl, 110 μl, 100 μl, 90 μl, 80 μl, 70 μl, 60 μl, 50 μl, 40 μl, 30 μl, 20 μl, or 10 μl. The lens implant 12 is made of a suitable transparent material, particularly selected from flexible materials, such as materials known in the art for manufacturing intraocular lenses, such as silicone or hydrophobic and hydrophilic acrylic materials, hydrogels, or collagen polymers.

[0037] The lens implant 12 has a convex posterior surface with a curvature (or simply posterior curvature) that is shaped to match the curvature of the posterior surface of the capsule 13. In some embodiments of the lens implant 12, the radius of curvature of the posterior surface varies in the range of 4 to 8 mm, particularly in the range of 5.5 mm to 6 mm plus or minus up to 25% or 20% or 15% or 10% or 5%, or for example in the range of 4.6 to 7.5 mm or 5 to 7 mm, or approximately 6 mm.

[0038] The aforementioned radius of curvature specifically refers to the radius of curvature measured on or near the visual axis 11. The vicinity of the visual axis is defined as the range adjacent to the visual axis, within a solid angle of up to 10°, up to 20°, or up to 30° of the visual axis 11.

[0039] In some of these and other embodiments, the lens implant 12 has a maximum diameter 14, particularly a maximum outer diameter 14 measured from one outer surface to the other, which is at most equal to the length of the equatorial diameter 5 of the natural lens 1. Figure 2 As shown, the maximum diameter 14 is specifically perpendicular to the visual axis 11 of the eye and parallel to the equatorial diameter 5. Specifically, the maximum diameter 14 of the implant 12 is at most 98%, 95%, 90%, 80%, 70%, 60%, or 50% of the equatorial diameter 5 of the natural lens 1. In some of these and other embodiments, the maximum diameter 14 of the implant 12 is at least 50%, 60%, 70%, 80%, or 90% of the equatorial diameter 5 of the natural lens 1. In some embodiments, the maximum diameter 14 of the implant 12 has an upper boundary in the range of 5 to 12 mm, particularly 11, 10, 9, 8, 7, or 6 mm. In some of these and other embodiments of the implant, the lower boundary of the maximum diameter 14 of the implant is in the range of 3 to 7 mm, particularly 3, 4, 5, or 6 mm. Embodiments of lens implants having a maximum diameter 14 smaller than the equatorial diameter 5 of the natural lens do not enter the equatorial portion of the intracapsular space. Thus, the epithelial cells lining the equatorial region of the inner surface (also in the posterior part of the capsule) remain uncontacted by non-cellular structural material. The size of this uncontacted posterior equatorial portion increases as the maximum diameter 14 of the implant decreases.

[0040] In some of these and other embodiments, the lens implant 12 is made of a transparent material that is chosen to be deformable, thereby allowing the implant 12 to be introduced into the intracapsular space 3 through an opening in the lens capsule 13 in a folded or rolled-up state. In some embodiments, the lens implant is made of a flexible material that allows the implant to be introduced through an opening in the capsule 13, wherein the maximum diameter of the opening is in the range of 0.5 to 4 mm, particularly between 0.5 and 3 mm, and more particularly less than 3, 2, 1.75, 1.5, or 1.25 or 1 mm.

[0041] In some of these and other embodiments, the lens implant 12 is made of a transparent material that can expand by absorbing liquid. In these embodiments, the implant 12 has reached its expanded volume after being introduced into an aqueous environment within the lens capsule, and its properties include shape and size corresponding to those described herein for embodiments of implants not made of expandable materials. Expandable lens materials are known in the art. For example, commercially available implants (Acqua) made of hydrophilic acrylic polymers or hydrophilic / hydrophobic copolymers comprising hydroxyethyl methacrylate, vinylpyridinium ketone, and methyl methacrylate, such as those described by Mehta in http: / / www.boamumbai.com / journalpdfs / jan-mar2001 / tor-pedo.pdf, or, for example, those described in US4,834,753, or expandable hydrogels as described in WO2004 / 026928.

[0042] In some of these and other embodiments, the lens implant 12 has an anterior surface that is convex, flat, or concave. In some embodiments, the lens implant has a posterior convex surface and an anterior concave surface, with appropriately sized positive or negative menisci to achieve the desired refractive power (i.e., optical power). In some embodiments, the lens implant may be toric to correct astigmatism.

[0043] In some embodiments, the size and shape of the lens implant 12 are configured to provide refractive power suitable for vision at infinity, particularly in the range of -20 diopters to +60 diopters, depending on the needs of treating a particular patient. A lens implant 12 with zero refractive power is included because the lens implant, due to its shape conforming to the posterior medial surface of the capsule 13b, is independent of optical power correction. This allows for particularly effective treatment of secondary cataracts via laser surgery, whereby the area of ​​the posterior lens capsule can even be completely removed, while still maintaining the intracapsular space 3 enclosed by the perforated shell as described above.

[0044] In addition to illustrating an exemplary embodiment of an intraocular lens implant 12 placed in the posterior portion 3b of the intracapsular space 3, Figure 2An exemplary embodiment of the capsular filling composition 15 for intraocular surgery is also schematically shown, illustrating how the filling composition 15 can fill the intracapsular space 3 within the lens capsule 13. Clearly, the filling composition 15 fills not only the anterior portion 3a of the intracapsular space 3 but also a portion of the posterior portion 3b of the intracapsular space 3. Thus, it substantially replaces the remaining volume of the removed natural lens body 2 that was not replaced by the lens implant 12. The volume of the filling composition 15 can therefore be defined as a volume complementary to the volume of the implant 12, wherein the sum of the two corresponds to the volume of the natural lens body 2, or the volume of the intracapsular space 3 within the empty capsular bag.

[0045] Capsule-filling composition 15 is an aqueous composition and contains no noncellular structural components for permanently replacing the lens fibers included in the natural lens body. By filling the intracapsular space 3, capsule-filling composition 15 provides intracapsular pressure corresponding to the physiological intracapsular pressure prior to removal of the natural lens body. Unaffected intracapsular pressure is relevant to the eye's accommodative function.

[0046] The shape, geometry, and size of the lens implant 12 are not limited to Figure 2 The exemplary shape and size shown are not intended to be adapted very freely to fit the size and optical characteristics of a particular eye and produce the desired refractive power, provided that the lens implant 12 does not enter the anterior portion 3a of the intracapsular space 3, and in particular the lining of the epithelial cells 4 on the anterior inner surface 13a of the capsule 13 does not contact the implant 12 but rather the capsule filling composition 15.

[0047] In some of these and other embodiments, the capsule-filling composition 15 includes live cells. Such cells can be obtained, for example, from in vitro cultures or from tissue probes. In particular, the cells can be obtained from probes of the eye, and more particularly from probes comprising lens epithelial cells 4. Specifically, the cells added to the aqueous filler composition 15 are capable of developing lens fibers and / or secretory factors that promote the formation of lens fibers from the remaining or added lens epithelial cells.

[0048] In some of these and other embodiments, the cells included in the capsule-filling composition 15 are derived from autologous or allogeneic human eyes or from non-human eyes (particularly non-human mammalian eyes), and are cultured in vitro or not before being incorporated into the capsule-filling composition 15 or before being applied together with the capsule-filling composition 15 into the capsule interior space 3. Transplantation of allogeneic or non-human cells benefits from the fact that the contents within the capsule 13 are immune-forgivable, i.e., inaccessible to the immune system, and therefore not prone to immune rejection. In some embodiments, the capsule-filling composition is applied as a single component; in other embodiments, it is applied in several components, wherein these components may be applied simultaneously or at separate times, and they may have the same or variable composition.

[0049] In some of these and other embodiments of the capsule filling composition 15, it includes components specifically selected from the following: - Hyaluronic acid, - Growth factors, especially one or more of the following: fibroblast growth factors, including FGF-1 and FGF-2, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor I or II (IGF-I or IGF-II). - Anti-TGFβ blockers - Vitamin A.

[0050] The term "component" refers to a liquid or soluble compound suitable for establishing a physiologically aqueous environment within the lens capsule and may be based on, for example, a saline solution. The term "component" specifically includes active ingredients with active biochemical functions, such as those that actively promote the regeneration of clear lens fibrous tissue. For example, Lovicu et al. (Exp Eye Res, 142： (92, 2016) has shown that anti-TGFβ blockers promote the initiation of lens fiber formation by lens epithelial cells. Furthermore, several growth factors are known to stimulate lens regeneration, as reviewed by Henry (Int. Rev. Cytology, 2016). 228 (Reference: 195, 2001). Other components include nutrients, antibiotics, or other biochemical agents, such as osmotically active ingredients that regulate intracapsular pressure.

[0051] On the other hand, a kit is provided comprising a lens implant 12 as described above and a capsular filling composition 15. In some embodiments of the kit, the kit may include a collection of implants of different sizes and / or shapes and / or refractive powers for selection of an appropriate implant according to the patient's needs. The kit is adapted to completely replace the volume of the removed natural lens body 2, and in some embodiments of the kit, a lens implant and sample with a capsular filling composition of complementary volume may be provided, resulting in a volume substantially the same as that of the natural lens body. The filling composition 15 may promote the regeneration of lens fibers based on residual cells or based on added cells (particularly lens epithelial cells). In some embodiments, the filling composition may actively promote regeneration by including an active ingredient (particularly an ingredient selected according to the specific patient's needs). In some embodiments, the kit may include other suitable components for use or application to the eye during, before, or after surgery.

[0052] On the other hand, a method for providing a personalized intraocular lens implant 12 or a personalized kit is provided, the personalized kit comprising the intraocular lens implant 12 as described above and optionally further comprising a capsular filling composition 15 as described above. In some embodiments of the method of providing the kit, a step (a) of measuring the eye and a step (b) of selecting at least one implant 12 are included. In step (a), in particular, the axial length of the cornea and / or lens and / or eye is determined. The axial length of the eye or eyeball is defined by the distance between the anterior and posterior poles of the eyeball. Steps (a) and (b) may be performed at different times, particularly prior to surgery, for example, several weeks prior to surgery, and particularly up to one or two months prior to surgery. This measurement method is possible without requiring invasive or surgical procedures on a human or animal. Further embodiments of the method of providing a personalized lens implant or kit in step (a) rely on providing measurements obtained from an external source.

[0053] Methods for measuring the size of the eye and lens capsule are known in the art (see, for example, WO2011 / 02068). Biostatistical methods include ultrasound biostatistics, such as laser interferometric biostatistics (also known as optical biostatistics), which has been routinely used in recent years for the treatment of cataracts and refractive errors. An alternative method known in the art is partially coherent interferometry. Commonly used and commercially available exemplary eye biometers include Zeiss's IOL Master and HaagStreit's Lenstar system.

[0054] In some embodiments of the method of providing a personalized kit, in an additional step, the composition of the filling composition 15 is adapted to the needs of a particular patient. In some embodiments, the filling composition 15 is tailored, for example, by adding autologous cells or by selecting allogeneic live cells and / or specific or active ingredients. In some embodiments of the method of providing a personalized kit having a filling composition including cells, the cells may be cultured in vitro, for example for expansion according to procedures known in the art. The filling composition may be provided in the kit with all components premixed. Alternatively, the filling composition may be provided in a number of portions, some of which may include components or cells added and mixed into the filling composition at a predetermined time prior to application of the filling composition to the patient, or components or cells applied to the intracapsular space as a separate part of the filling composition at the same or different times.

[0055] In some embodiments of the method, a preferred volume or volume range of a filling composition that is complementary to the volume of the implant is determined for use in introducing intracapsular space.

[0056] By providing a personalized kit comprising one or more implants 12, or in some embodiments by additionally including a filling composition 15, the implant or kit is advantageously adapted to the patient’s specific needs, for example, at an appropriate time prior to surgery.

[0057] While presently preferred embodiments of the invention have been shown and described, it should be clearly understood that the invention is not limited thereto, but may be practiced and implemented differently in other ways within the scope of the appended claims.

Claims

1. An intraocular lens implant (12) for placement in the posterior portion (3b) of an intraocular space (3) after removal of the natural lens body (2) from the lens capsule (13) of the eye, the eye having an equatorial diameter (5) between the two equatorial poles (6) of the natural lens (1), the intraocular space (3) being divided into an anterior portion (3a) and the posterior portion (3b) along the equatorial diameter (5). in, The intraocular lens implant (12) is formed from a single component and made of a suitable non-cellular, transparent material. The size of the intraocular lens implant (12) is configured to ensure that the anterior portion (3a) of the intracapsular space (3) is free of non-cellular structural material. The intraocular lens implant (12) does not contain any other components formed of non-cellular structural materials or their components. The intraocular lens implant (12) comprises up to 40% of the volume of the removed natural lens body (2) or up to 40% of the volume of a natural lens body (2) of average size, and The intraocular lens implant (12) has a convex posterior surface with a curvature shaped to fit the posteroinner surface (13b) of the lens capsule (13).

2. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be up to 35% of the volume of the natural lens body (2).

3. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be up to 30% of the volume of the natural lens body (2).

4. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be up to 25% of the volume of the natural lens body (2).

5. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be up to 20% of the volume of the natural lens body (2).

6. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be up to 15% of the volume of the natural lens body (2).

7. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be at most 10% of the volume of the natural lens body (2).

8. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be at most 5% of the volume of the natural lens body (2).

9. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to be at most 2% of the volume of the natural lens body (2).

10. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 120 μl.

11. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 110 μl.

12. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 100 μl.

13. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 90 μl.

14. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 80 μl.

15. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 70 μl.

16. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 60 μl.

17. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 50 μl.

18. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 40 μl.

19. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 30 μl.

20. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 20 μl.

21. The intraocular lens implant (12) according to claim 1, wherein, The size of the intraocular lens implant (12) is set to include a volume of up to 10 μl.

22. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The radius of curvature of the posterior surface of the intraocular lens implant (12) is in the range of 4 to 8 mm.

23. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The radius of curvature of the posterior surface of the intraocular lens implant (12) is in the range of 4.6 to 7.5 mm.

24. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The radius of curvature of the posterior surface of the intraocular lens implant (12) is in the range of 5 to 7 mm.

25. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The radius of curvature of the posterior surface of the intraocular lens implant (12) is 6 mm.

26. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 98% of the equatorial diameter (5) of the natural lens (1).

27. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 95% of the equatorial diameter (5) of the natural lens (1).

28. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 90% of the equatorial diameter (5) of the natural lens (1).

29. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 80% of the equatorial diameter (5) of the natural lens (1).

30. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 70% of the equatorial diameter (5) of the natural lens (1).

31. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is up to 60% of the equatorial diameter (5) of the natural lens (1).

32. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at most 50% of the equatorial diameter (5) of the natural lens (1).

33. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at most equal to the length of the equatorial diameter (5) of the natural lens (1).

34. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is within a range of 12 mm at the upper boundary.

35. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at least 50% of the equatorial diameter (5) of the natural lens (1).

36. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at least 60% of the equatorial diameter (5) of the natural lens (1).

37. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at least 70% of the equatorial diameter (5) of the natural lens (1).

38. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at least 80% of the equatorial diameter (5) of the natural lens (1).

39. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is at least 90% of the equatorial diameter (5) of the natural lens (1).

40. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The maximum diameter (14) of the intraocular lens implant (12) is within a range of 3 mm at the lower boundary.

41. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is in the range of 0.5 to 4 mm.

42. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is in the range of 0.5 to 3 mm.

43. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is less than 3 mm.

44. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is less than 2 mm.

45. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is less than 1.5 mm.

46. ​​The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The transparent material is selected to be deformable, thereby allowing the intraocular lens implant (12) to be introduced into the intracapsular space (3) in a folded or rolled-up state through an opening in the lens capsule (13), wherein the maximum diameter of the opening is less than 1 mm.

47. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The anterior surface of the intraocular lens implant (12) is also convex, or the anterior surface is flat or concave.

48. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The size and shape of the intraocular lens implant (12) are configured to provide refractive power suitable for vision at infinity.

49. The intraocular lens implant (12) according to any one of claims 1 to 21, wherein, The size and shape of the intraocular lens implant (12) are configured to provide refractive power suitable for vision at infinity, having a refractive power that is suitable for the size of the eye in the range of -20 diopters to +60 diopters.

50. A capsule-filling composition (15) for use in intraocular surgery to fill the intraocular space (3) after the natural lens body (2) has been removed from the lens capsule (13) of the eye. in, The filling of the intraocular space (3) is accompanied by the introduction of an intraocular lens implant (12) according to any one of claims 1 to 49. The introduced volume of the capsule-filling composition (15), together with the volume of the intraocular lens implant (12), provides a reconstruction substantially corresponding to the volume of the removed natural lens body (2), or provides a reconstruction of the volume of a natural lens body (2) of average size. The capsule filling composition (15) is an aqueous composition and does not contain any non-cellular structural material or its components for replacing lens fibers.

51. The capsule filling composition (15) for intraocular surgery according to claim 50, comprising cells capable of developing lens fibers.

52. The capsule-filling composition (15) for intraocular surgery according to claim 50, comprising cells capable of developing lens fibers, obtained from a probe of the eye.

53. The capsule filling composition (15) for intraocular surgery according to claim 50, comprising cells capable of developing lens fibers, obtained from a probe comprising lens epithelial cells (4).

54. The capsule-filling composition (15) for intraocular surgery according to any one of claims 51 to 53, wherein, The cells are derived from the patient's own or a foreign human eye or from a non-human eye.

55. The capsule-filling composition (15) for intraocular surgery according to any one of claims 51 to 53, wherein, The cells are derived from human eyes (either autologous or allogeneic) or from the eyes of non-human mammals.

56. The capsule-filling composition (15) for intraocular surgery according to any one of claims 50 to 53, wherein, The capsule filling composition (15) comprises an ingredient selected from the following: - Hyaluronic acid, - Anti-TGFβ blockers - Growth factors, - Vitamin A-like substances.

57. The capsule-filling composition (15) for intraocular surgery according to any one of claims 50 to 53, wherein, The capsule filling composition (15) comprises an ingredient selected from the following: - Hyaluronic acid, - Anti-TGFβ blockers - One or more of the following: fibroblast growth factors, including FGF-1 and FGF-2, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor I or II (IGF-I or IGF-II). - Vitamin A-like substances.

58. A kit comprising an intraocular lens implant (12) according to any one of claims 1 to 49 and a capillary filling composition (15) for intraocular surgery according to any one of claims 50 to 57.

59. A method for providing an intraocular lens implant (12) according to any one of claims 1 to 49 after removal of a natural lens body (2), the method comprising the steps of: a. Provide eye measurements or perform measurements to provide results selected from the following. - The size of the natural lens (1) or cornea (10), or the length of the eye along the visual axis (11), - The optical power of the natural lens (1) or cornea (10), - The curvature of the posterior surface of the natural lens (1) or the radius of curvature of the posterior surface of the natural lens (1), which is the radius of curvature along the visual axis (11) or near the visual axis (11) of the natural lens (1). as well as b. Based on the results of step a, select an intraocular lens implant (12) according to any one of claims 1 to 49.

60. A method for providing the kit according to claim 58 after removal of the natural lens body (2), the method comprising the steps of: a. Provide eye measurements or perform measurements to provide results selected from the following. - The size of the natural lens (1) or cornea (10), or the length of the eye along the visual axis (11), - The optical power of the natural lens (1) or cornea (10), - The curvature of the posterior surface of the natural lens (1) or the radius of curvature of the posterior surface of the natural lens (1), which is the radius of curvature along the visual axis (11) or near the visual axis (11) of the natural lens (1). as well as b. Based on the results of step a, select an intraocular lens implant (12) according to any one of claims 1 to 49.

61. The method according to claim 60, wherein, In a further step, the composition of the capsule-filling composition (15) is adjusted by adding autologous or allogeneic live cells and / or by adding ingredients selected from: - Hyaluronic acid, - Anti-TGFβ blockers - Growth factors.

62. The method according to claim 60, wherein, In a further step, the composition of the capsule-filling composition (15) is adjusted by adding autologous or allogeneic live cells and / or by adding ingredients selected from: - Hyaluronic acid, - Anti-TGFβ blockers - One or more of the following: fibroblast growth factors, including FGF-1 and FGF-2, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor I or II (IGF-I or IGF-II). - Vitamin A-like substances.

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