Photochemically induced engagement of intraocular implants

Abstract

An ocular implant and a method for implanting such an ocular implant inside an eye includes an optical portion and at least two polymer haptics for fixation of the ocular implant to tissue inside an eye. At least one portion of the haptics contains a photoinitiating agent delivery component. A kit for implanting an ocular implant in an eye includes an ocular implant at least two polymer haptics; and additionally a photoinitiating agent for at least partially impregnating a first portion of the ocular element or a second portion of tissue in the eye; and, a light source for providing light of a wavelength adapted to excite the photoinitiating agent.

Claims

1. An intraocular lens (IOL) comprising: a central optical portion; at least two polymer haptics radially extending from said central optical portion for fixation of the intraocular lens to a capsular bag of an eye; wherein each of the at least two haptics comprises: (i) a curved plate defining a capsular-contacting surface, and (ii) a photoinitiating agent delivery means for providing a photoinitiating agent activatable by light for creating an irreversible photochemical bond between each polymer haptic and the capsular bag of the eye; a photoinitiating agent; means for making the intraocular lens to be in a stretched state in order to maximize contact between the at least two haptics and the capsular bag; and light guiding elements embedded in the means for making the intraocular lens to be in a stretched state, the light guiding elements sized and configured for providing light of a wavelength adapted to excite the photoinitiating agent for creating a photochemical bond between the intraocular lens and the capsular bag, wherein the photoinitiating agent delivery means comprises an outer surface of the polymer haptics being coated with the photoinitiating agent or comprising an outer layer of the polymer haptics where the photoinitiating agent is embedded, wherein the photoinitiating agent is a solution containing riboflavin or Rose Bengal, wherein the at least two haptics are made of a poly-hydroxyethylmethacrylate (pHEMA)-based polymer material.

2. The intraocular lens of claim 1, wherein the means for making the intraocular lens to be in a stretched state comprises at least one tension ring.

3. The intraocular lens of claim 1, wherein the means for making the intraocular lens to be in a stretched state comprises at least one balloon.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) To complete the description and in order to provide for a better understanding of the disclosure, a set of drawings is provided. Said drawings form an integral part of the description and illustrate an embodiment of the disclosure, which should not be interpreted as restricting the scope of the disclosure, but just as an example of how the disclosure can be carried out. The drawings comprise the following figures:

(2) FIG. 1 shows a cross-section view of an intraocular lens according to a first possible embodiment of the disclosure;

(3) FIG. 2 shows a perspective view of the intraocular lens of FIG. 1;

(4) FIG. 3 shows an embodiment of the removable capsular tension ring;

(5) FIG. 4 shows a section view of an intraocular lens according to a second possible embodiment of the disclosure;

(6) FIG. 5 shows a perspective view of the intraocular lens of FIG. 3;

(7) FIG. 6 is a diagram showing the influence of the radiation exposure times and irradiance on the strength of the bond between the ocular implant and the capsular bag; and

(8) FIG. 7 is a diagram showing the loads per photobonded area that produced breakage of the capsule-pHEMA bonding in air and in a nitrogen environment.

DETAILED DESCRIPTION OF THE DRAWINGS

(9) FIGS. 1 and 2 show an ocular implant 10a according to a first possible embodiment of the disclosure, which is designed to engage the capsular bag using photobonding.

(10) The ocular implant 10a comprises a deformable lens with a central optical portion 11 and a number of haptics 12a—six in this preferred embodiment—, which are uniformly distributed along an equatorial region of the central optical portion 11 of the lens. These haptics 12a extend radially from the edge of the central optical portion 11, and comprise free ends in the shape of transverse curved plates in order to facilitate the transfer of the ciliary muscle forces to the lens.

(11) In this first preferred embodiment, the haptics 12a contain a number of small microfluidic channels 13 through which a photosensitizer can flow from the lens or haptics towards an external convex surface 121a of the haptics 12a and a portion of the capsular bag that is to be in contact with the lens 10a, in order to stain them.

(12) The haptics 12a are made of a pHEMA-based polymer material and the photosensitizer applied through microfluidic channels 13 is Rose Bengal.

(13) The ocular implant further comprises a removable capsular tension ring 14. This tension ring 14 is a cylindrical flexible body having a manipulation hole 141 at each of its ends. The tension ring 14 is arranged in the internal concave portion 122a of some of the haptics 12a or all of them, and is used to stretch the ocular implant 10a so as to apply pressure to the haptics. This maximizes contact between the haptics 12a and the capsular bag.

(14) Additionally, and as shown in detail in FIG. 3, the removable capsular tension ring 14 is attached to a probe 19 so that light can be transmitted through the probe and into the tension ring 14 so that it is capable of guiding light along the its entire length, and release the light required for photobonding in specific sites throughout its outer perimeter, including irradiating areas of the haptics 12a in contact with the capsular bag. In this preferred embodiment the light used has a green wavelength.

(15) In the case shown in the drawings the capsular tension ring 14 is removable, but it is also possible that the tension ring is not removable but it can be deactivated once the light has been irradiated and the photobonding has been achieved.

(16) The capsular tension ring shown in FIGS. 1 and 2 has two manipulation holes 141 at its ends. It is also possible that it has one or more manipulation hooks—not shown in the drawings—which are also valid for manipulating the ring.

(17) FIGS. 4 and 5 show an ocular implant 10b according to second possible embodiment of the disclosure, which is designed to engage the capsular bag using photobonding.

(18) The ocular implant 10b comprises a deformable lens with a central optical portion 11 with a number of haptics 12b—six in this preferred embodiment—, which are uniformly distributed along an equatorial region of the central optical portion 11 of the lens. The haptics 12b in this embodiment also extend radially from the edge of the central optical portion 11, and comprise free ends in the shape of transverse curved plates in order to facilitate the transfer of the ciliary muscle forces to the lens.

(19) In this case, an external convex surface 121b of the haptics 12b is coated with a photosensitizer, which is shown as shaded in FIG. 4.

(20) The haptics 12b are made of a poly-hydroxyethylmethacrylate (pHEMA)-based polymer material and the photosensitizer coating the external surface 121b of the haptics is Rose Bengal.

(21) The ocular implant further comprises one or two removable torus-shaped inflatable balloons 15, similar to a balloon catheter, with embedded fiber optics 16 along the outer edge of the balloon 15. Although not shown in the drawings, it is possible that the balloon is transparent and that the fiber optics is embedded inside the balloon instead of being embedded or extending along the perimeter of the balloon.

(22) The one or two balloons 15 are arranged in the internal concave portion 122b of the haptics 12b, and are used both to stretch the implantable device 10b so as to apply pressure to the haptics and to provide contact and light distribution as explained below.

(23) The inflation of the balloon or balloons 15 is controlled externally by means of a cannula 17. Upon inflation, the balloon 15 stretches the implantable device 10b and presses its haptics 12b against the capsular bag, to provide close contact between the haptics 12b and the capsular bag needed for photobonding.

(24) The embedded fiber optics 16 guides light injected by the cannula 17, and releases light throughout its perimeter, thereby irradiating areas of the haptics in contact with the capsular bag.

(25) In a preferred embodiment of this ocular implant 10b, the balloon 15 contains micro-pores (not shown in the figures) that release air or oxygen during inflation, so as to facilitate the oxygen-requiring photochemical reaction.

(26) In either case, the balloons 15 are de-inflated and removed after photobonding. The light guided into the fiber optics has a green wavelength.

(27) The following example illustrates an experimental procedure followed for implanting a body made of a polymer material to the capsular bag by photobonding.

(28) Capsular bags were obtained from freshly enucleated New Zealand albino rabbit eyes, less than 12 hours post-mortem. A circular section of the anterior capsule of the largest possible diameter (7-10 mm) was removed from the eye under an ophthalmological surgical microscope, using capsular scissors and immersed in a buffered saline solution BSS. Strips of capsule (5×7-10 mm) were cut and reserved for testing in the buffered saline solution.

(29) The polymer material used was a copolymer of pHEMA and GMA, provided by Vista Optics Ltd under the commercial name of Vistaflex Advantage +49. Samples of the copolymer material were cut, using a precision optics diamond-fiber cutter into 5×10 mm rectangular strips, of 1 mm thickness. The water content of the material is 49% in a hydration state. Each piece was dehydrated and then rehydrated in a Rose Bengal 0.1% solution.

(30) The Rose Bengal 0.1% solution was prepared dissolving 0.01 g of commercial Rose Bengal sodium salt (provided by Sigma Aldrich) into 10 ml of a phosphate buffered solution (PBS).

(31) The custom-developed light delivery system used in this experiment consisted of a pumped all-solid-state green laser source (provided by CNI Tech, Co. Ltd, China), with a central wavelength of 532 nm and an output power of 1300 mW and 1100 mW at the end of the fiber. The fiber tip is placed in the focal point of a 150-mm focal length lens. The sample holder is placed one focal length after the collimating lens. The light delivery system has neutral density filters which allow changing the laser power density at the sample plane between 0.65 and 0.25 W/cm.sup.2.

(32) Capsular bag strips were stained in Rose Bengal by immersion in the Rose Bengal solution for 2 minutes. The capsular bag strips were placed and deployed on top of the pHEMA-GMA strips, so that about half of the capsular bag strip and polymer strip overlapped, and they were placed in the sample holder of the light delivery system. Exposure times ranged between 30 and 180 s, and laser irradiances between 0.25 and 0.65 W/cm.sup.2.

(33) The strength of the bonding was tested using uniaxial extensiometry. For this testing the capsular bag end and the pHEMA end were clamped in a custom-developed extensiometry system, provided with piezo-motors and load sensors. The different loads were achieved by displacing each arm in 0.1 mm-steps, and the load producing a breakage in the capsule-pHEMA bonding was measured.

(34) FIG. 6 shows the loads that produced breakage of the capsule-pHEMA bonding as function of irradiation time, for three different laser irradiances: 0.25 W/cm.sup.2 (curve 101), 0.45 W/cm.sup.2 (curve 102) and 0.65 W/cm.sup.2 (curve 103).

(35) As can be seen, increasing exposure time and laser irradiance levels increases the breakage point of the bond created. Exposure times higher than 90 s at all tested laser irradiance levels produced a secure bonding, since photobonding breakage occurs for loads significantly higher (more than a factor 5 in the experiments carried out) than the cilliary muscle forces acting on the lens zonulae and capsular bag in human eyes.

(36) The overlapped pHEMA/capsular bag area was 21 mm.sup.2, on average.

(37) The average bonding resistance (load per bonded area) was 1 g/mm.sup.2.

(38) At higher irradiances (0.65 W/cm.sup.2) photobonding breakage was never observed for exposure times higher than 30 s. Instead, for this irradiance the rupture was produced in the capsular bag, suggesting that the photobonding may introduce structural changes in the capsular bag, making it more brittle. Capsular bag breakage occurred at much higher loads (55 g for 0.65 W/cm.sup.2, 180 s exposure time) in tissue from pigmented rabbits than from New Zealand albino rabbits.

(39) The experiment was repeated for an irradiance of 0.45 W/cm.sup.2 and exposure times between 60 and 180 s in a nitrogen environment, by placing the capsular bag-polymer strip system in a chamber connected to a nitrogen pump.

(40) FIG. 7 shows the loads per photobonded area that produced breakage of the capsule-pHEMA bonding in air and in a nitrogen environment, for irradiance of 0.45 W/cm.sup.2 and different exposure times. For a direct comparison with the photobonding in air, the stress values are normalized by the photobonded area, which was on average 15.41±4.54 mm.sup.2 in the experiments in air, and 18.86±5.26 mm.sup.2 in the experiments in nitrogen. For all the exposure conditions, photobonding was significantly weaker in the nitrogen environment. For example, for a exposure time of 120 s breakage of the photobonding occurred for a stress per area 1.63 times higher in air than in hydrogen environment. Capsular breakage occurred in air for the longer exposure time. These results indicate that the presence of oxygen facilitates the photochemical processes involved in the capsular bag-polymer bonding.

(41) In another example an intraocular lens was bonded to a capsular bag by means of photochemically-induced bonding.

(42) This example illustrates the bonding of the haptics of a pHEMA-MMA intraocular lens to the anterior lens capsule, intraocularly, demonstrating the feasibility of the procedure intraocularly.

(43) Enucleated rabbit eyes were obtained less than 4 hours post-mortem. The cornea was cut, and the crystalline lens material was aspirated using a Simcoe cannula through a 5-mm diameter anterior lens capsulorhexis. A 2-plate haptic pHEMA-MMA Akreos lens (by Bausch and Lomb®) was stained in a 0.1% Rose Bengal solution during 2 minutes, and then inserted in the capsular bag. An air bubble (1 ml approximately) was infused in the vitreous cavity of the eye using a 25-gauge needle. The air bubble created pressure between the capsular bag inner wall and the IOL and haptic plates. The whole eye was immersed in saline solution in a cuvette and the cuvette placed under the light delivery system. The cuvette was shifted laterally, such that the optical axis of the instrument was 2-mm-off centered from the IOL apex. The estimated peak irradiance was 0.25 W/cm.sup.2 at the location of one haptic and 0.05 W/cm.sup.2 at the location of the second haptic. Exposure time was 300 s.

(44) After exposure the IOL was cut in two pieces inside the capsular bag. Strong bonding was achieved between the anterior capsular bag the haptic of the lens that had been exposed to the higher irradiance, while no bonding was achieved between for the haptic of the lens that had been exposed to the lower irradiance.

(45) In an additional procedure in a different eye, the IOL implantation was done under similar conditions, but in this case the capsular bag was stained with a solution of 0.1% Rose Bengal using 30 gauge cannula during the hydro-dissection maneuver (injection of rose Bengal in the plane between the capsular bag and the lens cortex) after performing the anterior capsulorhexis. The IOL was then implanted through the capsulorhexis into the capsular bag. As in the former procedure, after exposure the IOL was cut in two pieces inside the capsular bag. Strong bonding was achieved between the anterior capsular bag and the haptic of the lens that had been exposed to the higher irradiance, while no bonding was achieved between for the haptic of the lens that had been exposed to the lower irradiance.

(46) In another setting the cornea and the iris were removed, and a scleral window was performed to expose the lens equator. Then the capsular bag was emptied through a 6-mm diameter capsulorhexis and the capsule was stained with Rose Bengal during the hydro-dissection maneuver. Then a piece of pHEMA re-hydrated in Rose Bengal was introduced through the rhexis and placed against the equator with a forceps. In that position irradiation was performed through the scleral window (0.65 mW/cm.sup.2, 150 s). Then a silicone tube was glued to the pHEMA piece with cyanoacrylate. To evaluate the strength of the photobonding the sclera and the silicone tube were clamped to the two arms of the stretcher. Strong photobonding was obtained, with capsular breakage occurring while capsular bag-pHEMA was still bonded. The estimated bonding resistance was 0.85 g/mm.sup.2.

(47) In this text, the term “comprises” and its derivations (such as “comprising”, etc.) should not be understood in an excluding sense, that is, these terms should not be interpreted as excluding the possibility that what is described and defined may include further elements, steps, etc.

(48) On the other hand, the disclosure is obviously not limited to the specific embodiment(s) described herein, but also encompasses any variations that may be considered by any person skilled in the art (for example, as regards the choice of materials, dimensions, components, configuration, etc.), within the general scope of the disclosure.