Cornea inlay, method for eye coloring, and method for manufacturing a cornea inlay

Abstract

The invention is directed to a cornea inlay for a human eye, wherein the inlay comprises a bi-ocompatible base material; and a coloring mimicking the optical appearance of the iris of a human eye. The invention is also directed to a method for altering the visible eye color of a human eye, comprising the steps of preparing a pocket in the cornea of the eye and inserting an implant into the cornea pocket, wherein the implant is configured as a corneal inlay that includes a coloring to simulate an iris as well as to a method for preparing a cornea inlay for a human eye, comprising the steps of providing a biocompatible base layer; applying a coloring to the base layer, the coloring mimicking the optical appearance of the iris of a human eye.

Description

[0001] O&P

[0002] P 70600 WO - 1 - 15.12.2025

[0003] Cornea inlay, method for eye coloring, and method for manufacturing a cornea inlay

[0004] BACKGROUND OF THE INVENTION

[0005] 1. Field of the Invention

[0006] The invention is directed to a cornea inlay, a method for eye coloring, and a method for manufacturing a cornea inlay.

[0007] 2. Description of Related Prior Art

[0008] Throughout human history, the desire to alter personal appearance has been a constant pursuit, seen in practices as varied as changing hair color or enhancing skin tone. Yet, despite advances in cosmetic and medical technology, eye color - the very defining feature of an individual's appearance - remains challenging to alter permanently and safely. While various solutions have been attempted, most options for eye color change are either temporary or pose significant risks.

[0009] Currently, colored contact lenses are the most accessible method for changing eye color. While they provide an effective temporary solution, these lenses have several limitations. For many users, wearing contact lenses over extended periods leads to discomfort, including dryness, irritation, and even infection. The requirement for daily handling and cleaning can also be inconvenient, particularly for individuals sensitive to foreign materials. Furthermore, improper lens care can increase the risk of severe eye infections, making contact lenses an im- perfect choice for long-term eye color change.

[0010] In response to these limitations, more permanent solutions have emerged, including kera- topigmentation and artificial iris implants. However, each of these medical procedures comes with its own set of challenges and potential complications: Keratopigmentation involves the injection or application of colored pigments directly into the corneal tissue to alter the eye's appearance permanently. The pigments are typically inserted via manual techniques or laser assistance, creating a colored layer within the cornea.

[0011] While this technique achieves lasting cosmetic effects, it presents significant risks. Uneven pigment distribution can lead to a patchy appearance or distortions in visual perception. Moreover, the pigments used, despite being designed for biocompatibility, may migrate within the corneal layers over time, potentially causing unintended color changes or visual aberrations. Incorrect pigment placement depth can lead to either excessive color saturation or insufficient color visibility, and any revision of pigment placement can be challenging, given the sensitive nature of corneal tissue.

[0012] Another permanent option involves the implantation of artificial iris devices within the eye. Originally developed as a medical solution for patients with traumatic iris damage or congenital aniridia (absence of the iris), these implants are also used to cosmetically alter the eye's appearance by mimicking a natural iris color.

[0013] However, iris implants carry a high degree of risk. Complications include increased intraocular pressure, which can lead to glaucoma, as well as corneal decompensation and cataract formation. The procedure is considered invasive and has led to adverse effects in a significant number of cases, making it an unsuitable choice for many patients seeking purely cosmetic eye color change.

[0014] Given these significant challenges and risks, the present invention aims to offer an innovative approach that overcomes the limitations of current permanent eye color alteration methods.

[0015] SUMMARY OF THE INVENTION

[0016] It is therefore an object of the present invention to provide a cornea inlay, a method for coloring a human eye, and a method for manufacturing a cornea inlay which involve less risks and which are more predictable in its outcomes. Also, a further object could be assuring reversibility of the procedure in case the client wants to change the color again or wants to go back to his / her original coloring. O&P

[0017] P 70600 WO - 3 - 15.12.2025

[0018] This object of the invention is achieved by a cornea inlay for a human eye according to independent claim 1.

[0019] The inventive cornea inlay for a human eye comprises a biocompatible base material and a coloring that mimics the optical appearance of the human iris. The inlay can be implanted in the cornea of the eye, particularly in the stroma of the cornea, in a procedure that involves standard eye surgery techniques allowing for a proven implanting procedure. By combining a highly biocompatible carrier with an optically effective coloring that is isolated from the surrounding tissue, long-term color stability is obtained while avoiding pigment migration or interaction with ocular structures; at the same time the inlay can be removed if a color change is desired, which preserves the reversibility of the procedure and enhances patient safety. This method may also advantageously used for improving the aesthetics of malfor- mations / scars / hazy areas or the like in the human cornea. Such visible aesthetic defect may be less visible or invisible after the implantation of the cornea inlay.

[0020] Preferably, the inlay has an annular geometry with a central, pigment-free opening. This configuration leaves the natural visual axis unobstructed, prevents unwanted refractive power or scattering, and preserves the natural aesthetic appearance.

[0021] Advantageously, the inlay comprises a radial incision. The slit enables the inlay to be folded or rolled for insertion through a small corneal access, thereby reducing the incision length and epithelial trauma.

[0022] According to an embodiment, the biocompatible base material contains at least one of a hydrogel, silicone hydrogel, poly-HEMA, polymacon, polyvinylidene fluoride or polysulfone. These materials offer high oxygen and water permeability, optical transparency and mechanical stability, so that irritation, hypoxia and haze are avoided even during long-term wear.

[0023] According to a preferred alternative embodiment, the biocompatible base material comprises biological stromal tissue obtained from a human or animal cornea. Native stromal collagen integrates biomechanically with the host cornea. Preferably, the coloring comprises pigments. The pigments are selected for a precise replication of natural iris colors and for an optimal biocompatibility and long-term stability.

[0024] It can be preferred that the pigments comprise titanium dioxide, iron oxides, chromium oxide green and / or ultramarine blue. These inorganic pigments show proven safety, are photo- chemically inert and guarantee color constancy over many years.

[0025] Preferably, the pigments are enclosed within the biocompatible base material. Encapsulation prevents pigment leakage into neighboring ocular tissues, ensures homogeneous color distribution and reduces inflammatory risks.

[0026] The object is also achieved by a method according to independent claim 6. The inventive method for preparing a cornea inlay comprises the following steps: providing a donor cornea, excising an annular stromal segment from said cornea and opening the segment along an incision so as to form an intrastromal pouch. The donor cornea graft can be autologous, i.e. the excised annular stromal segment may be re-introduced after coloring into the same cornea. Processing the explanted annular stromal segment ex vivo permits direct visual assessment, sterile handling and precise formation of the pouch, thereby ensuring consistent implant geometry. The geometry of the annular stromal segment can be selected according to the needs of the process. The general shape may be annular, but for handling or positioning purposes the shape may have a flat or the like to facilitate a reproduceable positioning.

[0027] It may be advantageous if the incision used to open the annular stromal segment is located in a peripheral region of the ring. A peripheral entry leaves the central optical zone structurally intact, which simplifies handling and preserves mechanical symmetry of the inlay. Alternatively, the incision may be located at any other area suitable for creating a pouch in which the pigments may be inserted.

[0028] Also, multiple incisions are created in the stromal segment to facilitate uniform pigment distribution. Distributed entry points prevent pigment aggregation, resulting in a homogeneous iris-like pattern and reducing the risk of color artefacts. A particularly preferred embodiment employs a femtosecond laser to excise the annular stromal segment. Ultra-short laser pulses generate microscopically smooth cut surfaces with minimal thermal damage and ensure sub-micrometer accuracy, facilitating exact repositioning of the explant after pigmentation.

[0029] Preferably, a pigment composition is introduced into the pouch ex vivo and the pigmented stromal segment is provided as the cornea inlay. External pigmentation allows uniform dispersion under direct observation and avoids intra-ocular contamination, yielding a color-accurate implant ready for surgery.

[0030] It is advantageous when the pigment composition comprises titanium dioxide, iron oxides, chromium oxide green and / or ultramarine blue. These inorganic pigments are biocompatible, photochemically stable and provide lasting chromatic fidelity.

[0031] Preferably, the pigmented stromal segment undergoes a cross-linking step and / or receives a top-layer coating so that the pigment composition remains securely enclosed. Such post-processing enhances mechanical robustness and prevents pigment leakage even under compressive or shear stress during blinking.

[0032] It can further be provided that the pigmented stromal inlay is stored in a sterile preservation solution prior to implantation. Cold-storage media maintain tissue hydration and optical clarity while ensuring sterility until the operative session.

[0033] The object is further achieved by a method according to independent claim 12. The inventive method for altering the visible eye color comprises the following steps: preparing a stromal pocket in the cornea and inserting, into the pocket, a cornea inlay as described above. This minimally invasive technique leverages established refractive-surgery tooling, ensures accurate positioning of the inlay and thereby shortens healing time and reduces visual side-effects. As already mentioned, the corneal inlay may be used to alter the coloring of the iris by implanting the colored inlay in the cornea. Also, malformations / scars / hazy areas or the like in the cornea may be aesthetically improved be the cornea inlay. Preferably, the stromal pocket is prepared with a femtosecond laser and / or by creating a corneal flap. Laser or flap techniques provide smooth pocket walls and precise depth control, enhancing seating stability of the inlay and limiting collateral tissue damage. As already mentioned above, the stroma pocket may be circular, but may also have features breaking circular symmetry for enhancing a rotationally invariant positioning of the inlay, if necessary.

[0034] Advantageously, one or more micro-incisions are prepared to facilitate insertion of the cornea inlay. Small entry ports minimize epithelial disruption, lower postoperative discomfort and speed up the healing process.

[0035] In this context, it is preferred that the insertion of the inlay is facilitated by preparing one or more micro incisions. These small openings enable precise placement of the inlay while minimizing trauma to the corneal tissue. In particular, one or more incisions may be used to insert the inlay as a whole. Alternatively, the inlay may be inserted in parts though one or more incisions. For example, the inlay may be comprised of two, three, four or more ring segments, the individual segments being inserted through corresponding incisions. Alternatively, the inlay parts may be inserted through one incision. Also, the inlay may be inserted through one incision and be unfolded by manipulation through another or the same incision.

[0036] Finally, the pigmented stromal inlay is re-implanted into the stromal pocket of the recipient cornea. Accurate re-implantation restores corneal contour and guarantees long-term positional stability of the colored ring, thereby maintaining the desired cosmetic outcome.

[0037] In an alternative embodiment, the biocompatible base material comprises a hydrogel, silicone hydrogel, or other clear biocompatible material. The mentioned materials ensure a good long-term wearability of the inlay, since the portions of the inlay getting into contact with the surrounding biological tissues are highly biocompatible. Also, the materials are designed to maintain a certain amount of water and thus minimize irritation of the eye.

[0038] A further embodiment specifies that the inlay material may include - without being limited to - poly-HEMA, polymacon, polyvinylidenfluorid,or polysulfone. These materials are well- known for their durability and transparency, which contribute to the inlay's longevity and its ability to mimic the natural iris without impairing vision. In a preferred embodiment, the pigments are enclosed within the biocompatible base material. This configuration prevents pigment migration, ensuring uniform color distribution and reducing the risk of visual distortions.

[0039] According to another aspect, the pigments are incorporated into the base material either before or during a polymerization step. This process ensures the pigments are securely embedded within the inlay, enhancing durability and reducing the likelihood of color fading over time.

[0040] According to a further embodiment, the coloring comprises a printed structure, in particular a film.

[0041] In particular, the printed structure could be arranged on a base layer or stacked between two layers.

[0042] According to an embodiment, the base material is formed in a layer shape. This allows for a uniform outer shape.

[0043] Alternatively, the base material has a mesh-like or sponge-like structure. The mesh-like or sponge-like structure allows for a high diffusion coefficient and a good nutrient transport through the inlay.

[0044] A particularly advantageous embodiment specifies that the inlay has a thickness ranging between 10 and 50 pm. This thin profile minimizes interference with the cornea's natural biomechanics while ensuring the inlay is virtually undetectable.

[0045] In the case of a biocompatible base material comprising biological stromal tissue obtained from a human or animal cornea, the thickness of the base layer may be 200 pm or less, e.g. between 20 pm and 200 pm, preferably between 50 pm and 150 pm.

[0046] According to a specific embodiment, the inlay includes a central, pigment-free opening aligned with the natural pupil. This alignment ensures unimpeded light transmission and preserves the user's visual acuity, addressing potential drawbacks of other cosmetic eye alteration methods. Alternatively, the inlay is designed such that an existing visual impairment is corrected or at least improved.

[0047] Further, in an embodiment the inlay is formed with a plurality of recesses that allow for a high diffusion coefficient and a good nutrient transport through the inlay.

[0048] According to an optimized method, the pocket is created in the corneal stroma at a depth of 100-300 pm, preferably between 100-200 pm, or less than 50% of the total corneal thickness. This precise placement ensures the inlay remains securely positioned without compromising the structural stability of the cornea.

[0049] The inlay used in the method corresponds to any of the aforementioned embodiments, ensuring that the procedural benefits align with the structural advantages of the inlay itself. Together, these features offer a holistic approach to eye color alteration that prioritizes safety, comfort, and aesthetic outcomes.

[0050] In an embodiment, the base layer could be printed on one side facing up and covered with a top layer. Thus, the two layers could comprise the same materials and could easily fit together. Alternatively, the material of the base layer could be different for the material of a top layer. This would allow to a combination of different materials, e.g. rigid and / or flexible.

[0051] In a preferred embodiment the method the step of applying the coloring comprises applying a pigmentation and / or a printed layer to the base layer.

[0052] Preferably, the step of applying the coloring comprises applying a top layer such that the pigmentation is enclosed. This ensures that the pigments of the pigmentation remain enclosed in the inlay and do not get in touch with the surrounding biological tissue.

[0053] The top layer may include the dame material as the base layer. Alternatively, the top layer may be a top coating or / and may comprise a different material composition than the base layer. O&P

[0054] P 70600 WO - 9 - 15.12.2025

[0055] BRIEF DESCRIPTION OF THE DRAWINGS

[0056] Various features and advantages of the present invention may be more readily understood with reference to the following detailed description taken in conjunction with the accompanying drawings in which:

[0057] Figs. 1 a, 1 b a cross-sectional and a top view of a first embodiment of an inlay;

[0058] Figs. 2a, 2b a cross-sectional and a top view of a second embodiment of an inlay;

[0059] Figs. 3a, 2b a cross-sectional and a top view of a third embodiment of an inlay;

[0060] Figs. 4a-4c top views of further embodiments of the inlay according to Figs. 3a, 3b;

[0061] Fig. 5 a schematic illustration of a human eye and an inlay to be implanted;

[0062] Fig. 6 a flow diagram of a method for altering the visible eye color of a human eye;

[0063] Fig. 7 a schematic illustration of a human eye and another inlay to be implanted;

[0064] Fig. 8 a cross-sectional view of a cornea of the human eye with an implanted inlay;

[0065] Figs. 9a-d a schematic illustration of a manufacturing method for an inlay according to a first embodiment;

[0066] Fig. 10a-c a schematic illustration of a manufacturing method for an inlay according to a second embodiment;

[0067] Fig. 1 1 a-d a schematic illustration of a manufacturing method for an inlay according to a third embodiment; and

[0068] Fig. 12a, 12b a cross-sectional and a top view of a fourth embodiment of an inlay;

[0069] Figs. 13a, 13b a cross-sectional and a top view of a fifth embodiment of an inlay;

[0070] Fig. 14 a flow diagram of a method for preparing a stromal based cornea inlay;

[0071] Figs. 15a, 15b a cross-sectional and a top view of a sixth embodiment of an inlay; O&P

[0072] P 70600 WO - 10 - 15.12.2025

[0073] Figs. 16-18 in a schematic diagram the inlay shown in Figs. 15a, 15b having different pouch incision designs.

[0074] Figs. 1a and 1 b illustrate an exemplary corneal inlay for a human eye for mimicking the optical appearance of the iris of a human eye. Fig. 1 b is a top view of the inlay 10, Fig. 1a a cross- sectional view along the dashed line l-l.

[0075] Inlay 10 comprises a biocompatible base material 12 forming the body of the inlay 10. In the base material 12, a coloring 14 is embedded. In the shown embodiment of Figs. 1a, 1 b the coloring 14 comprises pigments. Depending on the intended coloring the respective pigment or / and a combination of various pigments is used. The pigment / s may include inter alia titanium dioxide, iron oxides, chromium oxide greens or / and a ultramarine blue.

[0076] The base material is intended to be biocompatible.

[0077] In a first embodiment, the biocompatible base material comprises biological stromal tissue obtained from a human or animal cornea.

[0078] Alternatively or additionally, the base material may comprise one or more of the following materials: a hydrogel, a silicone hydrogel, a clear biocompatible material, poly-HEMA, and / or poly-sulfone. According to the mentioned material groups, it is either intended to provide a highly flexible, oxygen-permeable material with high water content or a rigid, gas permeable material. Independent of the material choice, the pigments are enclosed by the base material and thus do not get into contact with any surrounding biological tissue from the human eye.

[0079] Figs. 2a, 2b, 3a, 3b, and 4a-c illustrate different embodiments of a corneal inlay regarding the outer shape of the inlay 10. Figs. 1a, 1 b show an embodiment, in which the base material 12 forms a continuous body. The body is generally disc shaped. The disc 16 has an outer rim 18, a coloring zone 20 as well as a transparent inner section 22. In the embodiment illustrated in Figs. 1a and 1 b, the inner section 22 is part of the base layer 12, i.e. all light passing from the outside into the human eye has to pass through the transparent base layer 12 present in the inner section 22. O&P

[0080] P 70600 WO - 11 - 15.12.2025

[0081] The embodiment illustrated in Figs. 2a, 2b shows a different approach. Regardless of the layering of the inlay 210, the central portion 222 is material-free. Accordingly, the body of the inlay 210 has the shape of a disc with a center hole. All other properties of the inlay 210 are similar to that of Figs. 1a, 1 b.

[0082] Figs. 3a, 3b illustrate a further embodiment of an inlay 310. All features already disclosed in the previous embodiments receive the same reference numeral-added by 100-and not described again in detail to avoid unnecessary repetitions.

[0083] The basic body shape of the inlay 310 is similar to that of the embodiment illustrated in Figs. 2a, 2b with the exception that a cut 324 is provided connecting the outer rim 318 and the inner portion 322. The cut 324 is also shown in detail in Fig. 3a, illustrating a cross-sectional view along the dashed line Ill-Ill as shown in Fig. 3b. As can be seen in Fig. 3a, the end sections 326, 328 of the portions abutting at the cut 324 are designed such that-when seen in a top view-no visible gap regarding the coloring 14 is visible. To this end, the end sections 326, 328 overlap such that the embedded coloring 314 also overlaps.

[0084] Figs. 4a-4c illustrate embodiments also having cuts as described regarding the embodiment of Figs. 3a, 3b. Whereas the embodiment of Figs. 3a, 3b remains despite the cut in one piece, the embodiments of Figs. 4a-4c are cut in two, three, and four 4 pieces. The same or a similar overlapping technique as described with regards to Fig. 3a is also applicable to the inlays 410, 410', 410" of Figs. 4a-4c.

[0085] Although termed "cut", the manufacturing of the cut is not necessarily a cutting procedure - although this may be the case. In any case, a full enclosure of the embedded coloring / pig- mentation has to be insured. To this end, during manufacturing an appropriate cutting section may be provided. Alternatively, the separation may be part of the general manufacturing process.

[0086] Fig. 5 illustrates a method for altering the visible eye color of a human eye. The method is also described in corresponding Fig. 6. Fig. 5 shows a human eye 100. In the eye 100, the sclera 102, the cornea 104 and the transitional zone between the cornea 104 and the sclera 102, the limbus 106, is shown. O&P

[0087] P 70600 WO - 12 - 15.12.2025

[0088] In a first step (S600), a pocket 108 is created. The pocket 108 is prepared in a shape suitable for the inlay to be inserted into the pocket 108. In the case the base layer of the inlay being an autologous implant, the content of the pocket 108 may be used as the inlay after an ex- vivo coloring / pigmenting process as described with reference to Figs. 14-18. In the embodiment shown in Fig. 5, the inlay 310 as already described in detail with reference to Figs. 3a, 3b as well as later with reference to Figs. 14-18 is prepared for insertion. Accordingly, the pocket 108 has also the shape of a disc with a central recession 110. After the creation of the pocket 108 or at the same time, an incision 112 is created.

[0089] The pocket 108 and / or the incision 112 may be created by using, for example, a laser like a femtosecond laser.

[0090] The dimensions of the pocket 108 are chosen according to the actual size of the original iris of the eye 100 or by the size of the inlay 310, which is to cover the original iris of the eye 100 when seen from front.

[0091] The dimension of the incision 112 is chosen according to the size of the implanting device. For example, e.g. a cannula.

[0092] After the formation of the incision 112, the inlay 310 is inserted into the pocket 108 (S602). Depending on size and material of the inlay and of the pocket 108, a second incision may be required, but is not shown in the embodiment illustrated in Fig. 5. Also, it may be of advantage to not leave the recess 110 of the pocket 108, although the inlay 310 has a base layer free central portion 322. Further, depending on the actual situation, other inlays, such as the inlay 210 of Figs. 2a, 2b having no cut 324 may be preferred.

[0093] Also, during the insertion step it may be preferred to add additional liquids that may be injected into the pocket 108 to support the unfolding of the inlay 210 / 310. Depending on the situation, viscoelastic solutions may also be added.

[0094] Fig. 7 illustrates in a further embodiment the implantation of the inlay 410", consisting of four individual segments 430", 432", 434", 436". The four segments may be inserted by a single O&P

[0095] P 70600 WO - 13 - 15.12.2025 incision 112 however, additional incisions 114, 116, 118 may be used to insert the different segments and / or as an excess to the pocket 108.

[0096] Fig. 8 illustrates the situation after the implantation of the inlay, for example the inlay 210 as illustrated in Figs. 2a, 2b. The cornea 104 consists, from anterior to posterior, of the epithelium 102, Bowman's layer 122, stroma 124, Descemet membrane 126, and the endothelium 128. The epithelium covers the surface of the cornea 104 and has an approximate thickness of about 15 pm. The stroma 124 is the thickest layer of the cornea 104 and is usually about 460 pm thick.

[0097] In Fig. 8, the height, i.e. the thickness, of the drawing is exaggerated by 10 and is thus not proportional.

[0098] The inlay 210 is positioned in the cornea with the inlay being centered on the eye’s visual excess. The inlay 210 can be implanted in the cornea 104 at a depth of about 50% less of the cornea thickness measured from the anterior surface of the cornea 104. For example, a depth of 250 pm or less may be appropriate.

[0099] The thickness of the inlay 210 may vary according to the actual situation and may be for example between 10 pm and 50 pm. Depending on the circumstances, thicker inlays 210 in the range of 100 pm or more may be acceptable, in particular in the case of the base layer comprising biological stromal tissue obtained from a human or animal cornea.

[0100] Fig. 9 illustrates a manufacturing process for any of the aforementioned inlays 10, 210, 310, 410, 510. The process involves providing a biocompatible base layer material 12 (see Fig. 9a). The base layer material 12 may comprise a hydrogel or other clear bio-compatible material. Exemplary materials may include Lidofilcon A, poly-HEMA (hydroxy ethyl methacrylate), polysulfone, silicon hydrogel.

[0101] After the formation of the biocompatible base layout 12, a coloring 14 is applied. The coloring 14 may be applied manually or may involve the use of printer. Coloring 14 may comprise a variety of pigments. The pigments may comprise titanium dioxide, iron oxides, chromium oxide green, and ultramarine blue. The pigments may be applied directly to the base layer 12 O&P

[0102] P 70600 WO - 14 - 15.12.2025 or may already be encapsulated in the material or a matrix. The encapsulating material may comprise poly-dimethyl siloxane (PDMS), acrylate polymers, e.g. poly-methyl methacrylate (PMMA), polyvinylidenfluorid (PVDF), and / or HEMA based hydrogel - see Fig. 9b.

[0103] In a next step (see Fig. 9c), the top layer 15 is provided over the coloring layer 14. The top layer 15 may be of the same material as the base layer 12 and is applied such that the coloring layer 14 is fully enclosed by either the top layer 15 or the base layer 12. As a result (see Fig. 9) the coloring 14 is fully encapsulated and does not get in contact with any biological tissue present in the eye. The layer 15 is as transparent as the base letter 12 is. In case that the inlay has no central recess / hole, the transparency of the base layer 12 and the top layer 15 is chosen such that the impact on the visibility of the eye is reduced as much as possible. For example, the pigments can be integrated into the matrix of the base layer material 12 / 15 during the process of polymerization. Alternatively or additionally, the pigments are bonded with cross linker monomers such as ethylene glycol dimethacrylate during the polymerization of the top layer 15 and / or of a base layer 12. The size of the particles of the pigments may be between 20 and 100 nm to provide a uniform color distribution and to minimize light scattering effects.

[0104] Figures 10a-10c illustrate a different embodiment of the method of manufacturing an inlay. In a first step (see Fig. 10a), a bio-compatible base layer is provided. In a second step (Fig. 10b), the coloring 14 is provided on the base layer. Those two steps closely correlate to that of the previously described embodiment with Figs. 10a, 10b. In a third step (see Fig. 10c), a top layer 17 is provided covering / enclosing the coloring 14. The top layer 17 is more of a coating, i.e. it covers the coloring 14 completely, but does not fully integrate with the base layout 12. However, a complete enclosure of the coloring 14 and the pigments enclosed therein is achieved.

[0105] Figures 11 a-11d illustrate a further embodiment of manufacturing an inlay.

[0106] In a first step (see Fig. 11a), a base layer 12 is provided. In a second step (see Fig. 11 b), the base layer 12 is structured. The structuring process may be an integral part of providing the O&P

[0107] P 70600 WO - 15 - 15.12.2025 base layer, e.g. by an injection molding process, by an additive manufacturing process, for example 3-D printing, or by a subtractive manufacturing process like milling or the like.

[0108] In the next step (see Fig. 11c), the coloring is added to the structured portions of the base layer 12. Thereby, the coloring has different thicknesses and provides an impression of depth. This allows the inlay to give a more natural impression of an iris.

[0109] Finally, the coloring 14 is covered either by a top layer 15 integrating with the base letter 12 or alternatively by a top coating having a smaller thickness.

[0110] Figures 12a, 12b and Figs. 13a, 13b illustrate further embodiments of a corneal inlay 1210, 1310. The illustration shown in Figs. 12a, 12b and 13a, 13b are intended to show structural features of the biocompatible base material 1212, 1312. The features shown can be combined freely in any way with the features of the embodiments shown in Figs. 1a-5 as previously described.

[0111] Fig. 12b is a top view of the inlay 1210, Fig. 12a a cross-sectional view along the dashed line XII-XII. The basic body of the inlay 1210 comprises a plurality of recesses 1240. The distribution and the dimensions of the recesses 1240 is chosen such as to optimize a propagation of any nutrients relevant for the corneal structures is possible in the required amount in order to maintain a healthy metabolism of the corneal structures. The dashed line is intentionally oriented along a series of recesses 1240. In the cross-sectional view of Fig. 12a it can be seen that the recesses allow a free passage of any metabolistic substances, e.g. by diffusion. The otherwise layer-like structure of the body of the inlay 2110 allow for the required coloring of the inlay 1210 as already described in the previous embodiments.

[0112] The ratio of the recesses / passages 1240 in relation to the area without recesses / passages 1240 is chosen such that the transport of metabolic substances is optimized without detracting from the visual impression of the inlay 1210. Thus, the shown ration is for demonstra- tiona l / illustrative purposes only. The actual recess dimensions and distribution may differ from the one shown in Figs. 12a, 12b. Also, an uneven distribution of the recesses 1240, varying diameters, and / or a varying diameter along the passage may be of advantage. O&P

[0113] P 70600 WO - 16 - 15.12.2025

[0114] Fig. 13b is a top view of the inlay 1310, Fig. 13a a cross-sectional view along the dashed line XIII-XIII. The basic body of the inlay 1210 is not that of a rigid body, but is instead of a meshlike or sponge-like structure. The mesh-like structure may be the result of weaving, knitting, or the like of threads or fibers of a biocompatible material. Also, other manufacturing methods for establishing a closed compound of threads / fibers may be used. For example, the fibers may be stuck together and undergo a thermal treatment for clustering the fibers together.

[0115] The fibers / threads may have a respective coloring, e.g. pigments enclosed in the fiber / thread, or may be colored after the manufacturing of the inlay body. In this case, a second step for enclosing the pigments, e.g. by coating the colored body, may be applied.

[0116] In any case, the resulting inlay 1310 is intended to have a very good diffusion coefficient allowing for a physiological transport of nutrient through the inlay 1310.

[0117] The same holds for a sponge-like structure. The sponge-like structure may be the result of a 3D-printing process (bioprinting): Biocompatible materials such as hydrogels, collagen or artificial polymers (e.g. PHEMA) can be used to print fine porous structures that resemble the natural cornea.

[0118] Alternatively, the inlay may be the result of electrospinning. This technique involves spinning ultra-fine fibers made of biocompatible polymers (e.g. PLLA, PCL) into porous, sponge-like mats that can be used as implants.

[0119] Further, the inlay 1310 may be produced by a sol-gel process. This chemical process enables the production of porous structures made of bioglass or silicates that ensure light transmission and stability.

[0120] Also, the inlay 1310 may be produced by gas foaming, which is a gas incorporation into polymers that creates microporous sponge structures that can serve as a scaffold for cell growth.

[0121] Alternatively or additionally, the following methods could be used to create highly permeable structures for an inlay: O&P

[0122] P 70600 WO - 17 - 15.12.2025

[0123] Phase Separation: In this process, porous membranes are produced by phase separation. The resulting pores are microscopically fine and enable a controlled exchange of substances.

[0124] Decellularized Scaffolds: Biological tissue is freed from cells by decellularization, whereby the extracellular matrix is retained. Such structures are highly permeable and biologically compatible.

[0125] Figure 14 schematically illustrates a workflow for a method for preparing a stromal-based cornea inlay, and Fig. 15b shows a top view of a sixth embodiment and Fig. 15a a cross-sectional view along the dashed line XV-XV in Fig. 15b of such a stromal based cornea inlay.

[0126] At the outset (S1400) a fresh donor cornea 1500 - in the case of an allogenic donor cornea - is positioned on a sterile workbench and kept in a temperature-controlled preservation medium so that physiological hydration and pH are maintained. In the case of an autologous coloring process, the human eye of the patient is prepared according to standard preparation procedures for cornea surgery or other similar procedures.

[0127] In step S1402 an annular stromal segment 1510 is excised with a femtosecond laser or an equivalent micro-keratome. The outer and inner diameters correspond to the target iris diameter and the natural pupil. In the case of an autologous cornea procedure, the stroma segment 1510 will later be re-introduced into the remaining pocket. In the case of an allogenic donor cornea, the outer contour of the segment can be designed in such a way that rotation of the transplant is prevented.

[0128] The laser parameters of the femtosecond laser are chosen to produce microscopically smooth cut faces free of thermal damage.

[0129] The freed ring, i.e. the annular segment 1510, is removed from the stroma pocket. In the autologous case, it is preferred to form and remove the annular segment with at least damage to the surrounding stroma tissue as possible. Therefore, in the case of a femtosecond laser formed pocket in the cornea 1500, the extraction is performed by providing a corresponding incision into the cornea through which the annular segment may be removed. In this context, it may be advantageously to provide a radial incision 1511 (see Fig. 15b). The incision 1511 O&P

[0130] P 70600 WO - 18 - 15.12.2025 opens the closed annular segment 1510 such that the segment may be extracted through a small incision in the outer side of the cornea 1500.

[0131] In the case of a flap formed in the cornea 1500, the provision of the incision may be done in a later step outside of the cornea 1500. In this case, the annular segment 1510 is lifted with a suitable tool and transferred to balanced-salt solution to prevent desiccation.

[0132] Subsequently (S1404) the annular segment 1510 is opened along a tangential peripheral incision. Figures 16 to 18 illustrate various examples of incision geometries.

[0133] Figure 16 shows the annular segment or inlay 1610 having the incision 1611 dividing the overall ring such that the annular segment 1610 may easily be reintroduced into the cornea of a patient. The incision 1611 is performed perpendicular to the plane of the annular segment 1610, i.e. to the plane of the drawing. The incision 1612, for creating a pouch inside of the annular segment 1610, is performed parallel to the plane of the annular segment 1610, indicated by a diagonal hatching in Fig. 16 (and the like in Figs. 17, 18). As can be seen in Fig. 16, the incision 1612 is performed all around the circumference of the annular segment 1610 and extends almost all the way to the center of the annular segment 1610. A small area 1613 is left uncut, thus connecting the upper and the lower half of the annular segment 1610 after the incision 1612. The area of the incision 1612 will, in a later step, be filled with pigments.

[0134] Figure 17 illustrates an alternative embodiment for an incision design. The incision 1712, as shown in figure 17, also extends all around the circumference of the annular segment or inlay 1710 but leaves two areas 1715 uncut in addition to the inner area 1713, which also remains uncut. This enhances the stability of the inlay 1710 after the incising process. Besides the uncut areas 1715, the overall design is equivalent to that shown and described in Fig. 16.

[0135] Figure 18 illustrates a further alternative embodiment of the incision geometry. The incision 1812, as shown in Fig. 18, extends all the way to the center 1822 of the annular segment 1810, but leaves a small uncut region 1815 on the opposite side of the incision 1811. With this geometry, the upper side of the annular segment 1810 can be fully folded to the side to allow for optimum access to the pouch created by the incision 1812. O&P

[0136] P 70600 WO - 19 - 15.12.2025

[0137] In general, the incision design depends on many parameters, in particular also on the individual situation relating to the donor cornea and the receiving cornea, the preferences of the surgeon performing the surgery, on the tooling available for performing the incision as well as the pigmentation.

[0138] The incisions 1612, 1712, 1812 may be applied in a single cut, or may be a series of several separate cuts to open up the interior of the annular segment 1510. As already mentioned, the incision may observe a certain distance to the inner section 1522 to leave the inner section 1522 intact. Alternatively, the incision 1512 may go through the inner section 1522 and only leave a hinge in the outer circumference of the annular segment 1510.

[0139] After making the incision 1612, 1712, 1812, the now partially separated parts of the annular segment 1510 are opened, e.g. by gently dilating the parts with micro-spreading forceps in order to create an intrastromal pouch 1514. The central optical zone remains mechanically intact so that symmetry is preserved. Alternatively, the parts separated by the incision 1612, 1712, 1812 may remain in loose contact, but be give access to introduce a tool for dispersing the pigments.

[0140] In step S1406 a sterile pigment dispersion - for example a mixture of titanium-dioxide and iron-oxide particles or any other suitable pigment composition - is injected into or dispersed in the pouch created by the incision 1612, 1712, 1812via a cannula or any other suitable tool until the pouch is filled as to the needs for creating a visible coloring to the annular segment 1510. Multiple punctures can be made to aid even distribution, and excess carrier fluid is aspirated.

[0141] If desired, the pigmented annular segment 1510 may then undergo a brief riboflavin-UV cross-linking treatment to enhance mechanical robustness without affecting optical clarity.

[0142] Finally (S1408) the completed inlayl 510 is transferred into a sterile screw-cap vial containing dextran-enriched preservation solution, labelled with donor identification, pigment composition and ring dimensions, and stored at four degrees Celsius until implantation. Processing all delicate steps ex vivo under direct visual control results in a homogeneously pigmented, mechanically stable and sterile cornea inlay that can be implanted according to the eye-color alteration method described above, e.g. with Figs. 5 and 6 while keeping the recipient cornea structurally uncompromised and minimizing postoperative risks.

Claims

O&PP 70600 WO - 21 - 15.12.2025CLAIMS1. A cornea inlay (10) for a human eye, comprising: a) a biocompatible base material (12); and b) a coloring (14) mimicking the optical appearance of the iris of a human eye.

2. The inlay of claim 1, wherein the inlay has an annular geometry with a central, pigment-free opening.

3. The inlay of claim 1 or 2, wherein the inlay comprises at least one radial incision.

4. The inlay of any of claims 1 to 3, wherein the biocompatible base material comprises biological stromal tissue obtained from a human or animal cornea.

5. The inlay of any of claims 1 to 4, wherein the coloring is enclosed within the base material.

6. A method for preparing a cornea inlay for a human eye, comprising the steps of: a) providing a donor cornea; b) excising an annular segment of stromal tissue from the donor cornea; and c) opening the annular segment along an incision so as to form an intrastromal pouch.

7. The method of claim 6, comprising the steps of; d) introducing a pigment composition into the pouch ex vivo; and e) providing the pigmented stromal segment as the cornea inlay.

8. The method of claim 6 or 7, wherein multiple incisions are created in the stromal segment to facilitate uniform pigment distribution.O&PP 70600 WO - 22 - 15.12.20259. The method of any of claims 6 to 8, wherein the pigment composition comprises titanium dioxide, iron oxides, chromium oxide green and / or ultramarine blue.

10. The method of any of claims 6 to 9, wherein the pigmented stromal segment undergoes a cross-linking or top-layer application step so that the pigment composition remains enclosed within the stromal tissue.

11. The method of any of claims 6 to 10, further comprising storing the pigmented stromal inlay in a sterile preservation solution prior to implantation.

12. A method for altering the visible eye color of a human eye, comprising the steps of: a) preparing a stromal pocket in the cornea of the eye; and b) inserting, into the pocket, a cornea inlay according to any of claims 1 to 5 or prepared according to any of claims 6 to 11.

13. The method of claim 12, wherein the stromal pocket is prepared with a femtosecond laser and / or by creating a corneal flap.

14. The method of claim 12 or 13, wherein one or more micro incisions are prepared to facilitate insertion of the cornea inlay.

15. The method of any of claims 12 to 14, wherein the pigmented stromal inlay is re-im- planted into the stromal pocket of the recipient cornea.

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