Patent Application
20210177573
This application has priority date of provisional patent application 139850140003008335 filed 12 Dec. 2019 Granted 19 May, 2020 Iran.
This invention is in the field of ophthalmology and relates to regenerating the cornea with applications in ectasia and keratoconus disease, devices, and methods for their treatment. It also relates to other modifications of cornea for correction of myopia and astigmatism and prevention or treatment of different eye disorders as well as cosmetic purposes.
A normal (emmetropic) eye focuses the image of distant objects on the retina at rest without accommodation. Such an eye creates a sharp vision for distant objects without effort. Any abnormality in the eye constitutes ametropia, a condition where the eye at rest is unable to focus the image of a distant object on the retina. The result is blurred vision.
Ametropia is any condition of myopia (nearsightedness), hyperopia (farsightedness), or astigmatism (cylindrical image distortion). It may come from deviations in geometry of the globe or cornea.
Keratoconus is a chronic progressive noninflammatory eye disorder caused by thinning of cornea and its irregular deformation. The cornea assumes a conical shape which induces ametropia, decreasing vision quality. Keratoconus is a common corneal disease, with a prevalence of approximately 1 in 500 to 2000 according to NIH information.
From a biomechanical viewpoint, the corneal tissue is a viscoelastic material that can change structurally and deform under a force such as intraocular pressure. In some cases, biomechanical structural changes related to keratoconus lead to progression of the disease.
Various treatments have been suggested for the management of keratoconus, including corneal collagen crosslinking (CXL), intrastromal corneal ring (ICR) implantation, and lamellar or penetrating keratoplasty.
CXL uses riboflavin drops combined with UVA light to strengthen the cornea and reduce the progress of Keratoconus.
ICR is generally a rigid implant made of a biocompatible material such as polymethyl methacrylate (PMMA). An ICR may be a full 360° circle, or a circular arc with arc lengths of less than 90° up to 355° called ICR segment. Two ICR segments with equal or different size may be used based on the severity and specific topography of the keratoconic eye. Usually, an ICR has one positioning hole at each end.
Lamellar and penetrating keratoplasties are interventions in which partial or total transplantation of the corneal tissue is performed to restore visual acuity.
ICR is primarily implanted through an incision in the cornea. A pocket is created inside corneal stroma to receive the ICR implant. The pockets may be created with mechanical devices such as PocketMaker microkeratome and Melles hook, or with femtosecond laser. Femtosecond laser is the preferred device as it provides much higher precision and is minimally invasive. The implanted ICR in the corneal stroma reduces the curvature of the cornea and improves visual acuity.
Cornea Implant, U.S. Pat. No. 8,092,526 describes a full circle flexible ring that can be squeezed in the ring plane to a smaller width for insertion into a corneal pocket through an incision in the cornea. After insertion, the ring springs back to a full circle inside the pocket. This ring is available in the market under the commercial name Myoring.
Prior art regarding the intrastromal implantation of PMMA rings for treatment of keratoconus and mild myopia is well documented under U.S. Pat. Nos. 4,452,235; 4,671,276; 4,766,895; 4,961,744; and 8,394,140 and others. All the related patents generally disclose implantation of a full circle or isolated ring segments inside the corneal stroma. Intacs, Keraring, and Myoring are typical ICR devices among numerous commercially available versions.
U.S. Pat. No. 6,051,023 describes an open ICR with one hole on one end and a few holes on the other end for adjusting the size and clipping of the ring after insertion into the cornea.
The cross section of existing ICRs is triangular (Ferrara ring, Myoring, Keraring brands), hexagonal (Intacs brand), or oval (Intacs SK brand). The intrusive geometry and sharp edges of the ICR profiles in relation to the cornea may be one reason for corneal melting.
Several studies report the effectiveness of the rings for improving visual acuity and reducing the refractive error and the mean keratometry (K) value in cases of keratoconus. In addition to the benefit of corneal remodeling and improvement in the optical quality of the cornea, some long-term studies report that ICR implantation may reduce the progression of keratoconus.
For example, the inventors of the present invention have shown that implantation of an ICR (355° Keraring) can regularize the corneal shape and reduce astigmatism in keratoconus patients with a clear cornea and contact lens intolerance (Jadidi, Khosrow, et al., Intrastromal corneal ring segment implantation (Keraring) 355° in patients with central keratoconus: 6-month follow-up, Journal of ophthalmology 2015).
The inventors of the present invention have also tried intrastromal corneal graft for treatment of keratoconus patients. The technique uses femtosecond laser to create a desirable corneal lenticule with precise diameter, thickness, and shape as well as an intrastromal pocket (Jadidi, K., & Mosavi, S. A. 2018, International Medical Case Reports Journal, p. 9-15, Keratoconus treatment using femtosecond-assisted intrastromal corneal graft (FAISCG) surgery: a case series).
In another study, Dragnea et al. developed Bowman layer transplantation for patients with advanced, progressive keratoconus aiming at corneal stabilization (Dragnea et al. Eye and Vision 2018 5:24, Bowman layer transplantation in the treatment of keratoconus). The technique consists of transplanting a donor Bowman layer into a mid-stromal pocket of a keratoconic cornea resulting in corneal flattening and stabilization against further ectasia. The treatment seems to halt the progression of keratoconus but has similar limitations in improving the corneal profile and visual acuity for the same reason of lack of tissue support addressed in Jadidi & Mosavi work above.
Soosan Jacob developed corneal allogenic intrastromal ring segments (CAIRS). CAIRS threads semi-circular donor inserts into channels cut in the patient's mid-peripheral stroma to reinforce and reshape the corneal surface. CAIRS may be done with or without CXL (Soosan Jacobs et al., J Refract Surg, 2018 May 1; 34(5):296-303, Corneal Allogenic Intrastromal Ring Segments (CAIRS) Combined With Corneal Cross-linking for Keratoconus).
Analysis of the ineffectiveness of corneal graft alone in treating keratoconus addressed above points to lack of limbal support and visible change in biomechanics of cornea. Stromal collagens are directional and extend end to end to limbus where they are linked to and supported by limbus. Any cross cutting of cornea permanently weakens it. Specifically, the permanent weakening of cornea due to vertical cutting in LASIK procedure is well documented and established. In keratoconus patients, the overall corneal structure is weak. The additional graft layer does not have the limbal support that is naturally available for stromal lamella and is free to readily deform and conform to the existing topography of the cornea. Therefore, it cannot modify the deformed cornea sufficiently to the desired shape. Gradually, the implanted graft bonds with the stroma, and therefore, the cornea becomes thicker but with nearly the same initial topography. The added graft may help reduce the progression of keratoconus rather than treating it.
Transplanting cornea is a solution to keratoconus but is considered as the last resort because it is complex and invasive, with chances of major complications during and after the operation.
An ICR applies radial outward forces at the boundary of the optical zone of the cornea to reshape it and reduce its curvature. These forces must be transferred through the cross section or thickness of the cornea in the form of shear and tensile forces and bending moment. Therefore, the amount of reshaping and refractive correction is limited by the viscoelastic characteristic of the already weak cornea itself. Also, the edge loading dictates the geometry or profile of the reshaped cornea which may not match the desired shape.
Although ICR has shown to provide some improvement in treatment of keratoconus and its progression, still there is need for ways to better reshape the cornea, further improve visual acuity, and halt the progression in keratoconus disorder. ICR devices can be only used for mild to moderate keratoconus. ICR is not a solution for all keratoconus cases, and therefore, development of new devices and methods can provide further help for treating keratoconus on a wider scale.
Therefore, the objects of the present invention include:
1. Transforming and enhancing the overall structure of the cornea by emulating its natural biomechanical system for increased corneal regularity and long term stability.
2. Providing distributed force within the cornea in addition to the localized boundary force of an ICR for improved reshaping of the cornea in both the amount and profile.
3. Providing potential for further conventional visual acuity correction and other corneal procedures and treatments.
4. Providing a treatment option for severe keratoconus over corneal transplantation.
5. Reducing the chance of corneal melting observed with existing ICR devices.
6. Providing a minimally invasive approach to deferring the complex, high risk and high maintenance cornea transplantation.
The present invention provides novel device and method to achieve all the objects of the invention discussed above. It corrects and slows down the deformation of cornea due to keratoconus or ectasia. Additionally, it allows to further correct refractive errors through conventional methods after the operation. And finally, the invention provides a viable minimally invasive approach to deferring cornea transplantation by regenerating the cornea and further allowing conventional treatments for other cornea related disorders.
The invention uses an ICR made of a polymer compatible with corneal metabolism such as polymethyl methacrylate (PMMA) in cooperation with a corneal graft to treat keratoconus and similar cornea disorders by adjusting the corneal topography and increasing its thickness.
The ring is a full circle with two spherical or aspherical side surfaces defining its thickness, and an inner and an outer rim defining its width. A plurality of holes, preferably 12, distributed around the ring pass through the side surfaces (
The side surfaces of the ring have a curvature in alignment with that of the cornea to prevent corneal melting at the cornea ring interface.
A natural or synthetic corneal graft lenticule is sutured to the ring via the holes such that it is uniformly stretched flat by the suture and fills the inside of the ring. The ring, the suture, and the graft together define a cohesive part acting in unison, named as ring graft in this invention (
The ring graft is inserted in the corneal stroma using superior scleral tunnel incision.
The diameter of ring holes is larger than that of the suture to allow biological interaction between cornea layers on the two sides of the ring and prevent corneal melting.
The cornea tends to align the flat graft with its curvature, which exerts a pull on the ring through the suture. The ring is fixed in location due to its interfacial relation with the cornea. Therefore, due to this interaction between the cornea and ring graft, the cornea stretches and curves the graft, while at the same time the graft reduces the curvature of the cornea (
This novel way of reducing the curvature of the cornea by the ring graft is in addition to the corneal curvature reduction performed with available conventional ICRs. Besides, it has the advantage of doing so by applying a distributed force within the cornea.
Additionally, the ring exerts an outward radial force that further reduces the curvature of the cornea as a conventional intracorneal ring.
The ring supports the graft circumferentially and promotes its bonding and unification with stroma. The supported graft reshapes and regenerates the cornea. As a major feature of the present invention, this results in increased thickness and strength of the cornea, which advantageously slows down the progress of keratoconus and provides post operation potential for further visual acuity improvement with refractive correction procedures such as customized PRK.
The regeneration of cornea afforded by this invention, provides a minimally invasive approach to deferring the complex, high risk, and high maintenance cornea transplantation. It advantageously opens possibilities for other conventional treatments in cornea disorders.
The ring with its distributed plurality of holes, the cornea aligned side surfaces, the ring graft, the method of preparation of ring graft, or the usage of ring graft in the cornea are exclusive features of the present invention.
The present invention provides novel device and method to achieve all the objects of the invention discussed above. It corrects and slows down the deformation of cornea due to keratoconus or ectasia. Additionally, it allows to further correct refractive errors through conventional methods after the operation. And finally, the invention provides a viable minimally invasive approach to deferring cornea transplantation by regenerating the cornea and further allowing conventional treatments for other cornea related disorders.
The materials, values, and measures in the description of the invention are preferred and typical. They can cover a range of values that is compatible with the biology, geometry, and profile of human cornea.
The descriptions, drawings, and claims of this invention as a whole define and clarify the novel and exclusive features of the invention.
According to
The thickness of ring 10 is 0.16 mm. The diameters of outer rim 11 and inner rim 12 are 8.40 mm and 7.60 mm respectively. The diameter of holes 15 is 0.30 mm.
Side surfaces 13 and 14 are preferably spherical or aspherical with a radius of curvature R and an angle C relative to the plane of outer rim 11. Angle C is approximately equal to the cornea angle at the location of ring 10, and therefore, depends on the diameter of outer rim 11, which defines the location of ring 10 relative to the cornea. As the diameter of outer rim 11 becomes smaller, angle C also becomes smaller. The recommended range of value for angle C is 20 to 40 degrees.
From a different perspective, ring 10 is a slice of a spherical or aspherical shell between two parallel planes defined by outer rim 11 and inner rim 12. This feature is intended to prevent the corneal melting issues in existing intracorneal rings.
Holes 15 are diagonally opposite to each other and have a count of 12. Holes 15 allow suturing of a corneal graft to ring 10. Additionally, they facilitate biological interaction and nutrition between cornea layers at the two side surfaces 13 and 14. This feature along with curvature R and angle C prevent corneal melting observed in conventional cornea implants.
Ring 10 with its plurality of distributed holes 15, spherical shell profile, or angle C, is a novel intracorneal ring exclusive to the present invention by itself, in relation to, or in cooperation with a human cornea.
Now, as shown in
Suture 18 stretches graft 16 uniformly toward inner rim 12 of ring 10 to a flat circular disk. The diameter of holes 15 is larger than that of suture 18 to allow biological interaction between cornea layers on sides 13 and 14 of ring 10 and prevent corneal melting.
The combination of ring 10, graft 16 and suture 18 work in unison together and define a cohesive and integral unit 20 named ring graft. Ring graft 20 is an exclusive means of the present invention by itself, in relation to, or in cooperation with a human cornea.
Graft 16 is a lenticule cut preferably with femtosecond laser and can be customized for diameter, thickness profile over its area, and shape according to the profile of keratoconus for individual patients. The customized thickness allows rebuilding the cornea to both an increased and uniform thickness across the cornea.
Graft 16 can be pure stroma or include the Bowman's membrane. Use of Bowman's membrane allows benefitting from its high stiffness and using same donor eye for two grafts.
Referring to
For insertion of ring graft 20 inside the stroma of cornea 21, a circular pocket is created inside the stroma. The pocket is created with Melles hook. Femtosecond laser may also be used instead.
Ring 10 reduces the curvature of cornea 21 by applying outward radial force to it as in existing intracorneal rings. Additionally, ring graft 16 further reduces the curvature of cornea through a separate and more effective mechanism. Ring 10 is fixed in the peripheral zone of cornea 21. Graft 16 is bound outside its normal flat plane by the curved middle zone of cornea 21. Ring 10 pulls graft 16 through suture 18 toward its flat shape while cornea 21 tends to pull graft 16 away and align it with its own curvature. As a result, cornea 21 and graft 16 reach an equilibrium curved state with reduced corneal curvature.
Ring 10 also applies a more effective tangential tension to the periphery 17 of graft 16 in contrast to the mere radial outward force at the ring-cornea interface in existing intracorneal rings.
This novel way of reducing the curvature of cornea 21 by the ring graft 20 is in addition to the corneal curvature reduction performed with available conventional intracorneal rings. Besides, it has the advantage of doing so by applying a distributed force at the interface of graft 16 with cornea 21.
Additionally, ring 10 exerts an outward radial force that further reduces the curvature of cornea 21 as a conventional intracorneal ring.
Ring 10 supports graft 16 circumferentially and promotes its bonding and unification with the stroma of cornea 21. The supported graft 16 reshapes and regenerates cornea 21. As a major feature of the present invention, this results in increased thickness and strength of cornea 21, which advantageously slows down the progress of keratoconus and provides post operation potential for further visual acuity improvement with refractive correction procedures such as customized PRK.
Daxer has shown that a full circle ring implant acts as an artificial limbus and strengthens the cornea (Daxer A., Cornea, p. 1493-1498, Volume 34, Number 11, November 2015, Biomechanics of Corneal Ring Implants). However, existing rings are structurally and isolated form the cornea. In contrast, ring graft 20 integrates and unifies structurally with the cornea, creating a thicker, and therefore, stronger cornea with graft 16, while additionally strengthening the regenerated and enhanced cornea with ring 10 as an auxiliary limbus linked to it through suture 18. In other words, the invention creates a new cornea with additional integrated limbal support.
The tight and stretched condition of graft 16 enhances its binding with the stroma and improves its biomechanical properties. One such property is cornea stiffness measured by a device such as Corvis ST via deformation of cornea under pulses of air. According to clinical data, the invention improved cornea stiffness by a factor of 2 to 3, which is an advantage over existing methods.
Currently, the only proven method of preventing keratoconus progress is CXL. The inventors suggest that the added thickness, strength, and limbal style support of cornea by ring graft 20 of the present invention should provide a definitive way to prevent the progression of keratoconus. The difference comes from the fact that CXL only creates additional links within the existing thin cornea structure.
Corneal irregularity causes glare and halo. Clinical studies by the inventors showed improvement in irregularity and reduction of glare and halo.
According to direct observation by the inventors, all existing ICRs may cause corneal melting. The present invention reduces the chance of corneal melting.
The inventors have also observed that reducing corneal curvature reduces astigmatism. The present invention should improve astigmatism better than existing intracorneal rings.
Currently, for sever keratoconus only transplantation is the norm. The present invention provides treatment for any level of keratoconus. The inventors successfully treated sever keratoconus cases in their clinical studies of the invention.
The regenerating of cornea afforded by this invention provides a minimally invasive approach to deferring the complex, high risk and high maintenance cornea transplantation. It advantageously opens possibilities for other conventional treatments in cornea disorders.
A ring graft stiffness measurement device may be used to adjust the stiffness of graft 16 via suture 18 to apply a desired pressure on cornea 21 for optimal curvature and vision correction of the cornea.
Three parameters, namely, thickness of ring 10, thickness of graft 16, and tension or stiffness of graft 16, can be varied for a desired refractive correction.
The device and method of the invention were successfully applied in severe keratoconus. The conditions and measurements of one eye are brought here in
The basics of preparing and installing ring graft 20 and the merits of the invention are described in previous paragraphs. The details of the method of the invention will be disclosed below.
The ring with its distributed plurality of holes or the cornea aligned side surfaces, the ring graft, the method of preparation of ring graft, or the usage of ring graft in the cornea are exclusive to the present invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 13985014000300833 | Dec 2019 | IR | national |
