Patent Application
20230174415
Exemplary arrangements relate to a method for producing an implant, in particular for inserting into an eye and in particular for inserting into the Schlemm's canal of an eye. Exemplary arrangements further relate to an implant produced according to this method.
Implants for insertion in the Schlemm's canal are known for example from WO 2010/072574. Such implants and the procedures for insertion thereof may benefit from improvements.
In use of an implant configured for insertion in the Schlemm's canal of an eye, the circular Schlemm's canal is exposed primarily at one location, and is gently expanded circularly with an inserted and flexibly designed microcatheter. At the same time or subsequently, a high-molecular-weight viscoelastic substance is injected. The exemplary implant which can be introduced into the lumen of the Schlemm's canal consists of a flexible, elongated tube with multiple openings or holes that communicate with an interior space. It may have at least one connecting part that is continuously oriented in the axial direction and with an arched surface, and in the inserted state is arranged to lie against the inner wall of the lumen for support. The individual openings and holes form a direct connection which is kept permanently open between the trabecular meshwork and the individual small collector channels of the distal outflow system, so that the natural transtrabecular outflow of the aqueous humor through the episcleral venous system into the blood circulation is assured.
In a healthy eye, the circulating aqueous humor (humor aquosus) drains from the posterior chamber to the anterior chamber and is discharged into the Schlemm's canal via the trabecular meshwork in the chamber angle (angulus iridocornealis), from there it is delivered into the blood circulation through the episcleral venous system. In pathological conditions of the eye, in particular when resistances occur due to closure of the Schlemm's canal caused for example by adhesion or the like, a continuous drainage of the aqueous humor, which is produced by the epithelium of the ciliary body and is constantly being renewed, is often no longer assured adequately, or even not at all. This can cause the intraocular pressure (IOP) to rise to such a degree that the circulation of blood to the retina and thus also the function thereof is impaired, wherein this functional impairment may lead to the eye disease known as glaucoma and may result in irreversible blindness in the affected eye.
For improving and maintaining the anatomical drainage of the aqueous humor, support elements embodied as elongated tubes with holes distributed over the surface thereof, or as elongated, tube-shaped net meshes or the like may be used as described in the publications (EP 0 898 947 A2 and EP 1 125568 A2), and can be inserted (or released) into the Schlemm's canal, which is exposed by creating an incision and folding back a scleral flap, and opened by injecting a high-viscosity medium. The elongated support elements are designed to facilitate the anatomically natural outflow of the circulating and permanently renewable aqueous humor from the anterior chamber through the trabecular meshwork and into the lumen of the circular Schlemm's canal, and from there into the blood circulation via the episcleral venous system.
In some arrangements a T-shaped implant which is attachable by means of a plate to the sclera in which an incision is made may be used as described in the document (US 2004/0210181 A1), and comprises a proximal piece of tubing that can be inserted operatively directly into the anterior chamber or through the trabecular meshwork into the anterior chamber, as well as two distal tube members which are arranged opposite each other on the piece of tubing and are insertable into the exposed Schlemm's canal. In order to avoid elevated intraocular pressure (IOP) in the case of a pathologically closed trabecular meshwork, with the implant which is designed to enable drainage, the constantly renewable aqueous humor is guided on an artificially created pathway by the proximal piece of tubing inserted into the anterior chamber, via the distal tubes directly into the Schlemm's canal, and from there into the blood circulation of the eye through the episcleral venous system. Further implants for the treatment of glaucoma, may be used as described in both documents (US 2005/0192527 A1 and 2007/0088432 A1), and which are either formable into an approximate T-shape with a thermal or mechanical shape memory effect or are constructed in an approximate T-shape without any shape memory effect.
These exemplary implants are each insertable with a proximal tube either directly or operatively through the trabecular meshwork into the anterior chamber and with two distal tubes arranged oppositely on the proximal tube into the Schlemm's canal, so that the constantly renewable aqueous humor is also transported along an artificially created pathway from the anterior chamber directly into the Schlemm's canal and from there into the blood circulation of the eye via the episcleral venous system.
The generally known canaloplasty method further offers the option of a circumferential dilation, in which the Schlemm's canal is expanded circularly by means of an inserted, flexible microcatheter and at the same time or subsequently a high-molecular-weight viscoelastic substance is injected by means of a “microscrew”. The microcatheter is then retracted again, and the circular Schlemm's canal is stretched towards the anterior chamber by suitable means, with a surgical thread, for example, resulting in an expansion of the trabecular meshwork and greater permeability with favourable transtrabecular drainage of the aqueous humor.
In exemplary arrangements various production steps and etching methods may be used. For example, Application DE 100 07 425 A1 includes a description of a method for producing an implant based on a photoresist. Here, the selectivity of the subsequent etching process is enabled a by chemical reaction in the photoresist. The method is used in the semiconductor industry when silicon chips are exposed to light.
Other exemplary production method steps may be used. For example EP 2 473 311 describes a method in which an opaque base material is used that facilitates material removal with a laser.
However, some known production methods share the disadvantage that they are relatively expensive for mass production, and the implants cannot be manufactured with a process reliability that assures consistent quality.
Exemplary arrangements provide a production method for producing an implant configured for insertion in the Schlemm's canal and also new implant configurations, with which such implants may be produced rapidly, inexpensively and reproducibly.
Useful results are provided in accordance with the methods recited in the claims hereof.
Alternatively a suitable implant may also be created additively in layers from powdered material by melting, or material dissolved in fluid is solidified by local heat input in the focus area in such a way that the implant is formed. It is useful when forming the implant by melting if a continuous wave laser is used, the radiation from which is substantially absorbed by the material. For example, a CO2 laser with a wavelength of 10 μm is suitable for this purpose.
It is useful if the implant is manufactured from a biocompatible material that is produced either additively or subtractively with laser radiation.
In producing an exemplary implant using SLE (Selective Laser Etching), the selectivity is achieved by non-linear absorption in a material that is intrinsically transparent for the wavelengths used (glass, sapphire, visible light). In the process, the absorption is enabled by exceeding a threshold intensity, which is situated at about 1010-1013 W/cm2 depending on the material and wavelength. At these intensities, the refractive index of the transparent material of the provided implant blank is non-elastic, that is to say it is altered permanently, and thus for the fluid etching media subsequently used (e.g., KOH) the etchability/etching rate are also altered compared with the unchanged material. Accordingly, this is a completely different process from the methods used hitherto for achieving the requisite selectivity.
Application DE 10 2015 115 958 A1 describes a special composition of glass constituents, which influence a cell population on the implant when used in some exemplary arrangements depending on the use case.
The exemplary subtractive process described has the advantage that local, sufficiently high intensities are able to alter an implant blank that is provided in such a way that the material can be removed from the blank in the regions and areas of the blank that are subjected to radiation in this manner, thereby giving rise to cavities in those places (e.g., by SLE=Selective Laser Etching).
In this context, the irradiated material can be eliminated directly or in a second, subsequent process, only at the sites where the exposure to the laser has altered the material correspondingly in such a manner that the second (etching) process removes the material, in a fluid etching step for example.
The implant of exemplary arrangements may be produced from various materials. Glass, sapphire or plastic are advantageous materials for the implant. A glass fibre or hollow glass fibre, which is preferably processed further with the SLE method, may also serve as starting material. In such case, the glass fibre may be shortened to a specific length before or after the treatment.
The wavelength of the laser radiation used in exemplary methods may have a value between 150 nm and 1800 nm, preferably 1064 nm or 532 nm or 334 nm or 266 nm.
Pulsed laser radiation is preferably used for laser etching.
The exemplary focal radius of the laser radiation should be between 1 μm and 100 μm, preferably about 5 to 10 μm. Useful values for the focal radius rF are in the range from 0.5 to 5 μm and in particular from 1 to 3 μm.
The pulse energy of the laser radiation may be in a range between 0.3 μJ and 3 μJ. Useful pulse energies have values in the range from Ep=0.1-1 J, for example, and in particular from 0.3 to 0.8 μJ. The pulse duration T may have a value from 0.5 to 5 ps and in some particular arrangements 0.8 to 2 ps.
The pulse frequency of the laser radiation may be in a range from 1 kHz to 1 MHz, wherein average output of the laser should be between 1 mW and a few Watts. Useful intensities I are in the range from 1012 to 1014 W/cm2 and in particular arrangements about 1013 W/cm2. For the repetition rate v REP, values between 10 kHz and 1 MHz and in particular arrangements between 50 kHz and 500 kHz are suitable. The average output Pquer then has a value for example of 1 mW to 1 W and in particular arrangements 100 to 500 mW. Ultimately, in some arrangements they may be for example approximately 1011 W/cm2×10−11 s×(5 μm)2.
In some exemplary arrangements the implant may be polished so that it has a smooth surface, with no notches which might make it more likely to break.
Laser radiation may be used for polishing the implant. In this case, for example a highly absorbable CO2 laser beam is suitable. The polishing should have the effect of smoothing the surface of the implant. This may provide the effect of preventing or at least reducing the notching effect, to increase fatigue strength under cyclic bending stresses and improve breaking resistance as well as providing greater elasticity and lower risk of breakage. A smooth surface also makes it easier to introduce the implant into the body, such as in particular the eye or the Schlemm's canal.
Alternatively or additionally, the implant may also be polished using an ion etching process in an ion etching process step.
An advantageous alterative process step provides that the implant is polished by Rapid Thermal Annealing (RTA). This is a furnace melting process at high temperatures and with short heating times. In some exemplary arrangements, very rapid heating is achieved with halogen lamps, followed immediately by very fast cooling. The heating may also be performed with a laser instead of or in addition to halogen lamps. This process may be carried out in a vacuum or in an inert gas atmosphere to avoid oxidation processes. In this context, time intervals for the heating and cooling and the temperatures used are harmonized with the special implant and the material thereof.
In some arrangements it is useful if the implant produced via the method has a hollow-cylindrical form and is liquid-permeable on opposite sides of the cylinder lateral surface. In such a case, the cylinder in cross-section may be elliptical or conical in shape.
If single openings to the hollow cylinder shape body are provided, the maximum cross-section thereof should be in the range from 10 μm to 50 μm. Of course if the openings are configured in a spiral, for example, the openings may also be larger. Moreover, openings with shapes other than circles or ovals are also possible.
The overall length of the exemplary implant may be from 0.1 cm to 5 cm, but in particular arrangements from 2 to 3 cm.
The diameter of the implant in the exemplary arrangements has a value between 30 μm and 300 μm, and in some arrangements about 100 μm. The exemplary implant may have a lattice-like structure, which extends longitudinally or also transversely to a longitudinal axis of the implant.
In some exemplary arrangements that the implant has a curved longitudinal axis.
An exemplary implant can be inserted in the Schlemm's canal of an eye at least as far as a quarter of the circumferential direction of the lumen of the circular Schlemm's canal. An insertion length of one quarter is advantageous. However, in some arrangements the implant may also be shorter, and may only be insertable into any fraction of the circumferential direction of the lumen.
In some exemplary arrangements the implant has a base body and a tip at one end of the body. This tip does not have to be sharp, and in some arrangements may also have a domed shape, for example. The radius of curvature of the tip in some arrangements may have a value of half the diameter of the implant and is thus in some arrangements is between 15 μm and 150 μm. The tip in some arrangements may also be asymmetrical. This makes it easier, for example in arrangements that have a configuration such as that of a dolphins snout, to insert the implant into a curved Schlemm's canal.
If it is desired to avoid having to mount or connect the tip separately, the tip may be produced in a single part with the base body.
In some exemplary arrangements the implant has struts which extend diagonally to the longitudinal axis and to the circumferential direction of the circumferential surface of the cylinder. In this way, a lattice structure may be created, in which a strut may also run transversely through a hollow cylinder.
In some exemplary arrangements the struts are helical, spiral or screw-shaped, and form at least part of the cylinder lateral surface. The formation of a helical circumferential line can make it possible to screw the implant into the eye along the circumferential line. In such a case, the struts may be designed as single or multi-thread helixes, as spirals with an open or porous filled core, or as screws.
In some exemplary arrangements the implant is opaque. For example, a coating or color may be applied in a process step after the implant has been manufactured, or a coloration may even be imparted during polishing, which enables visibility during a gonioscopy (chamber angle reflection with special lenses). This may also make it easier to reopen clogged openings in the implant, with a laser such as a Yag laser, if permeability disturbances are detected. A coloration such as a red end, may also serve as a mark to identify the manufacturer.
In some exemplary arrangements the implant has a longitudinal axis and is constructed symmetrically about said axis.
In order to facilitate the insertion of the implant in a lumen of a Schlemm's canal for example, some exemplary implant arrangements have a longitudinal axis and the cylinder lateral surface includes radially inward contact surfaces, which are arranged at an acute angle to the longitudinal axis. When such an implant is pushed into a lumen, the inclined contact surfaces press radially inwardly protruding subregions of the lumen outwards, while the implant is pushed into the lumen and in the lumen.
In some exemplary arrangements in which the implant has a cylindrical body a rod-shaped, spiral-shaped or sleeve-shaped insertion aid that can be connected detachably to the implant. An exemplary rod-shaped or spiral-shaped insertion aid may be screwed or pushed into a hollow cylindrical implant and the implant may be held in a sleeve-shaped insertion aid while it is inserted in the eye. During the insertion of the implant, it is connected to the insertion aid, and afterwards the insertion aid may be removed without changing the position of the implant. However, the insertion aid may also be used to push the implant into Schlemm's canal by positioning the insertion aid behind the implant.
In some exemplary arrangements the implant is spiral in shape, and the insertion aid has a correspondingly spiral-shaped counterpart, so that the implant can be screwed onto the insertion aid and, after insertion, the insertion aid may be unscrewed from the implant by rotating.
In some exemplary arrangements the spiral-shaped counterpart of the insertion aid may form an essentially smooth cylinder lateral surface with the cylinder lateral surface of the implant, when the implant is screwed on.
In some exemplary arrangements, the insertion aid may also be longer than the cylinder lateral surface, and it may have a handle which makes it possible to move and preferably even rotate an end of the insertion aid located inside the implant.
In the following discussion a medical procedure for inserting an implant produced via the exemplary methods will be explained. Of course these described approaches are exemplary and other approaches, arrangements and processes may be used.
At this point, it is noted that
The Schlemm's canal 15 is oriented circularly around the cornea and, as shown schematically and on a larger scale in
In
The section 15″ of the Schlemm's canal 15 that is opposite the already treated section 15′ can also be treated in the same way and expanded hydraulically in a circular direction in a manner known per se with a mirror-inverted probe inserted into the Schlemm's canal 15.
During the expansion of the Schlemm's canal 15 described above, openings (not shown) that may arise in the wall are opened and stretched at the same time with the hydrophilic fluid 29, with the result that these collectors are also reactivated and ensure the outflow of the aqueous humor. Instead of the hydrophilic fluid, a suitable, biologically compatible gaseous medium or also a mixture of the hydrophilic fluid and the gaseous medium can also be used to expand Schlemm's canal.
As is represented schematically in
As an alternative to the “ab externo” route into the eye via the scleral access, the implant may also be inserted “ab interno” tangentially to the Schlemm's canal through a Clear Cornea access. This would allow minimally invasive glaucoma surgery with an incision of about 2 mm and less. For this purpose, the Schlemm's canal is opened at the point opposite the incision by a minimal opening of the trabecular meshwork and from here the exemplary implant is pushed tangentially into the possibly pre-stretched Schlemm's canal. This is shown in
In the case of an exemplary implant having a screw shape, the base body may be in the form of a band and wound around a longitudinal axis as shown in
However, as shown in
Thus the exemplary arrangements described herein provide improved operation and capabilities, eliminate difficulties encountered in the use of prior methods and devices, and attain the useful results that are described herein.
In the foregoing description, certain terms have been used for brevity, clarity and understanding. However no unnecessary limitations are to be implied therefrom because such terms are used for descriptive purposes and are intended to be broadly construed. Moreover the descriptions and illustrations herein are by way of examples and the new and useful features, relationships and methods are not limited to the exact features, relationships and method steps that have been shown and described.
It should be understood that the features, relationships and method steps associated with one arrangement can be combined with features, relationships and method steps from another arrangement. That is, features, relationships and method steps various arrangements can be combined into other arrangements. The new and useful scope of the disclosure is not limited only to the arrangements that have been shown and described.
Having described features, discoveries and principles of the exemplary arrangements, the manner in which they are carried out, constructed and utilized, and the advantages and useful results attained, the new and useful features, devices, methods, approaches, elements, arrangements, parts, combinations, systems, processes, equipment, operations, methods and relationships are set forth in the appended claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2020 002 231.6 | Apr 2020 | DE | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/DE2021/000057 | 3/30/2021 | WO |
