Patent Application
20210251744
This invention relates to light adjustable intraocular lenses, and more specifically to composite intraocular lenses that can be adjusted by illumination.
The techniques of cataract surgery have been experiencing continuous, impressive progress of late. Subsequent generations of phacoemulsification platforms and newly invented surgical lasers keep increasing the precision of the placement of intraocular lenses (IOLs) and keep reducing the unwanted medical outcomes. Also, present generations of IOLs, based on soft acrylate materials, deliver very good optical outcomes, and numerous additional medical benefits, including ease and control of the implantation process, and an advantageous haptic design.
Nevertheless, some types of challenges remain even with the latest generation of devices and IOLs. One of them is that, in spite of surgeons carrying out the most careful pre-surgical diagnostics to determine the optimal IOL to be implanted, in a notable percentage of cases the post-surgical medical outcomes are less than optimal. This can be caused by a variety of factors, including an uneven healing process of the incisions tilting or moving the implanted IOL, or an imperfect modeling of the eye, among others.
A noteworthy breakthrough has been achieved recently by the development of lenses that can be adjusted non-invasively after the cataract surgery. These lenses involve light sensitive materials that photopolymerize upon activation by an irradiation. Irradiation with a carefully designed radial profile initiates the photopolymerization with a corresponding radial profile, which, in turn, leads to the IOL changing its physical shape and therefore, its optical power. These light adjustable lenses hold great promise to adjust and eliminate the residual post-surgical misalignments and to fine tune “the last diopter” of the IOLs post-surgically and non-invasively.
However, the present generation of these light adjustable lenses can be further improved still. Areas of possible improvements include optimized material properties that could ease the challenges of the implantation, as well as better haptic designs.
Therefore, there is an unmet medical need for intraocular lenses that deliver the advantages of both today's regular acrylate IOLs, and that of the light adjustable IOLs, while minimizing the less desirable aspects of their performance.
A composite light adjustable intraocular lens comprises an acrylic diffractive intraocular lens, having a diffractive structure and haptics; and a silicone light adjustable lens, attached to the acrylic diffractive intraocular lens. The diffractive structure produces constructive interference in at least four consecutive diffractive orders corresponding a range of vision between near and distance vision, wherein the constructive interference produces a near focal point, a distance focal point corresponding to the base power of the ophthalmic lens, and an intermediate focal point between the near focal point and the distance focal point and wherein a diffraction efficiency of at least one of the diffractive orders is suppressed to less than ten percent. In some embodiments, a composite light adjustable intraocular lens can include an acrylic diffractive intraocular lens, having a diffractive structure and haptics; and a silicone light adjustable lens, attached to the acrylic diffractive intraocular lens, wherein the diffractive structure includes a plurality of annular diffractive steps and four consecutive diffractive orders; wherein the composite light adjustable intraocular lens produces a near focus, an intermediate focus, and a distance focus, each corresponding to a different one of the four consecutive diffractive orders; and the plurality of annular diffractive steps of the diffractive structure are configured such that one of the four diffractive orders is suppressed and at least a portion of the energy associated with that suppressed diffractive order is redistributed to one of the near focus, the intermediate focus, and the distance focus.
Existing light adjustable intraocular lenses are often made of silicone-based polymers, such as poly-siloxanes and corresponding copolymers. Existing non-light-adjustable intraocular lenses are often made of various acrylates. The limitations (L) and the benefits (B) of these two classes of IOLs include the followings.
(L1) The elastic constants of silicone-based IOLs are often stronger, or stiffer, than that of some other IOUs, and therefore these silicone-based IOLs are often “springy” in comparison. One consequence of this springiness is that, during the JOE implantation process, the folded silicone-based IOLs unfold quite fast as they are pushed out from the surgical inserter hand piece into the eye. This quick unfolding of the silicone-based IOLs can make the control of the insertion and the proper alignment of the silicone-based IOLs somewhat challenging for a surgeon during surgery.
(B1) In contrast, acrylate-based IOLs have softer elastic constants, and thus unfold slower during the insertion. This aspect allows the surgeon to exercise more control over the insertion of acrylate IOLs.
(L2) The design of silicone-based IOLs is often three-piece: the two haptics are often separately fabricated and subsequently inserted into the central lens body. This design feature increases manufacturing costs, may lead to a higher rate of haptics misalignment during manufacture, and to separation of the haptics from the IOL lens body during the insertion.
(B2) In contrast, some acrylate-based IOLs manage these challenges by having a one-piece design, where integrated haptics are formed from the same lens material and with the same molding step as the central lens body of the IOL. Such one-piece designs have lower manufacturing costs, deliver good haptics alignment with the lens body, and reduce the risk of haptic separation from the lens body during insertion.
At the same time, the presently known acrylate-based IOLs are not light adjustable. These non-light adjustable, often acrylate-based IOLs have drawbacks on their own. These include the followings.
(L3) When surgeons plan a cataract surgery, first they perform careful and extensive diagnostics of the cataractous eye. Based on this diagnostics, the surgeons determine the optimal placement, alignment and optical power of the IOL. However, as discussed previously, the IOLs often end up away from their planned optimal placement, possibly tilted or misaligned relative to the plan. This can happen for a variety of causes, such as uneven development of ocular tissue after the surgery.
(B3) Light adjustable IOLs offer a profound solution for this misplacement and misalignment problem. Once the IOL is implanted and settled in the capsular bag of the eye after surgery, a post-surgical diagnostics can be carried out to determine the unintended shifts in alignment and placement of the implanted IOL. The results of this post-surgical diagnostics can be used to determine what corrections of the IOL can compensate the misplacement and the misalignment of the implanted IOL. This post-surgical determination can be used to perform a light adjustment procedure to bring about the determined IOL corrections in the implanted light adjustable IOL.
(L4) The above misalignment problem is particularly acute for toric IOLs, where the implantation targets the elimination of a cylinder in the eye. For toric IOLs, an unintended rotation of the toric IOL axis by only 10 degrees after implantation can cause about 30% loss of efficiency. E.g. a nominal 3D cylinder of a toric IOL can be reduced to an effective 2D cylinder if the cylinder axis ends up rotated by only 10 degrees during or after implantation.
(B4) Light adjustable IOLs can be implanted without any preformed toric cylinder. After the implantation, when the IOL settled and stopped its unintended rotation, the surgeon can apply an illumination to form a cylinder in the settled. IOL, with its axis oriented exactly in the planned or targeted direction. Thus, light adjustable IOLs are capable of avoiding the possible loss of efficiency induced by unintended misalignments of the cylinder axis of toric IOLs.
This document describes intraocular lenses that combine the benefits (B1)-(B4) of the above two classes of IOLs. and therefore have the potential to overcome and to avoid the limitations (L1)-(L4) each class of IOLs has on their own. Additional benefits of various embodiments will be also articulated below.
In some embodiments, the IOL 110 can be designed, or selected, to deliver the majority, or the entirety, of the intended optical power of the CLA IOL 100. In such embodiments, the light adjustable lens 120 can be designed only to provide the corrections and adjustments the surgeon anticipates may become necessary after the CLA IOL 100 settles in the eye with some unintended misalignment. Since the role of the light adjustable lens 120 in such embodiments is only to provide a correction of 1D-2D of optical power or cylinder, it can be a much thinner lens than in non-composite light adjustable IOLs, where all the optical power is generated by the light adjustable material. The CLA IOL embodiments that include only a corrective light adjustable lens 120 can therefore involve a much thinner light adjustable lens 120. The adjustment and lock-in of the light adjustable lens 120 in such a CLA IOL 100, described in relation to
The light adjustable lens 120 can be designed to provide a vision correction up to 2D, in other embodiments, only up to 1D. In some embodiments, either the IOL 110, or the light adjustable lens 120 can be a meniscus lens.
Concerning the chemical composition, in acrylate embodiments, the IOL 110 can include a monomer, a macromer, or a polymer, any one of which can include an acrylate, an alkyl acrylate, an aryl acrylate, a substituted aryl acrylate, a substituted alkyl acrylate, a vinyl, or copolymers combining alkyl acrylates and aryl acrylates. In some IOL 110s, the alkyl acrylate can include a methyl acrylate, an ethyl acrylate, a phenyl acrylate, or polymers and co-polymers thereof.
In some embodiments, the chemical composition of the IOL 110 can include a fractional mixing of the chemical composition of the light adjustable lens 120. Such an IOL 110 can include silicone-based monomers or macromers, forming polymers or copolymers, and possibly crosslinkers with the acrylate, an alkyl acrylate, an aryl acrylate, a substituted aryl acrylate, a substituted alkyl acrylate, a vinyl, or copolymers combining alkyl acrylates and aryl acrylates.
In some embodiments, a monomer, a macromer, or a polymer of the IOL 110 can have a functional group that can include a hydroxy, amino, vinyl, mercapto, isocyanate, nitrile, carboxyl, or hydride. The functional group can be cationic, anionic or neutral.
In some embodiments, the light adjustable lens 120 can include a first polymer matrix, and a refraction modulating composition, dispersed in the first polymer matrix, wherein the refraction modulating composition is capable of a stimulus-induced polymerization that modulates a refraction of the light adjustable lens 120. The first polymer matrix can include a siloxane based polymer, formed from macromer and monomer building blocks with an alkyl group, or an aryl group.
In some embodiments of the composite light adjustable intraocular lens 100, the first polymer matrix can include a fractional mixing of at least one of an acrylate, an alkyl acrylate, an aryl acrylate, a substituted aryl acrylate, a substituted alkyl acrylate, a vinyl, and copolymers combining alkyl acrylates and aryl acrylates. These can form at least one of polymers and copolymers with compounds of the first polymer matrix.
The above embodiments, where the IOL. 110 includes a fractional mixing of a material of the light adjustable lens 120, and where the light adjustable lens 120 includes a fractional mixing of a material of the IOL 110, can be formed to increase the compatibility of the materials of the lenses 110 and 120, thereby increasing the mechanical, physical and chemical robustness of the CLA IOL 100.
Embodiments of the light adjustable lens 120 can also include a photoinitiator, to absorb a refraction modulating illumination; to be activated upon the absorption of the illumination; and to initiate the polymerization of the refraction modulating compound. In some embodiments, the photoinitiator of the light adjustable intraocular lens 120 can also include an ultraviolet absorber.
Embodiments of light adjustable lenses 120 have been described in substantial detail in the commonly owned U.S. Pat. No. 6,450,642, to J. M. Jethmalani et al., entitled: “Lenses capable of post-fabrication power modification”, hereby incorporated in its entirety by reference.
In step 101b, the exposure to the adjusting light causes the photosensitive macromers to polymerize with a radial profile, determined by the radial profile of the adjusting light.
In step 101c, the unpolymerized macromers diffuse to the central region where the photosensitive macromers photopolymerized previously. This causes a swelling of the light adjustable lens 120 in this central region. (In complementary processes, where the radial profile of the illuminating light in more intense towards the peripheral annulus of the light adjustable lens 120, the unpolymerized macromers diffuse outward to the peripheral annulus, causing the swelling of this peripheral annulus.)
Still in step 101c, the swelling can be followed by applying a lock-in light with an essentially uniform radial profile and greater intensity to polymerize all remaining macromers. In step 101d, this lock-in causes the light adjustable lens 120 to reach and to stabilize a shape that is swollen in its center, and therefore has a light-adjusted optical power. The above is only a very brief summary of the light adjustable lenses and their light adjustment procedure. A much more detailed explanation is provided in the incorporated U.S. Pat. No. 6,450,642, to J. M. Jethmalani et al.
In some embodiments, the IOL 110 and the light adjustable lens 120 are adapted to retain a chemical separation even after they are attached. This chemical separation can be achieved, e.g., by employing a refraction modulating composition in the light adjustable lens 120 that is not soluble in the materials of the IOL 110, and thus it does not diffuse into the IOL 110 from the light adjustable lens 120, in spite of the mobility of its constituent macromers in the first polymer matrix of the light adjustable lens 120 itself.
As mentioned before, one of the advantages of combining the IOL 110 that can be acrylic-based, with the light adjustable lens 120 that can be silicone-based is that an elastic constant of an acrylic IOL 110 can be softer than a corresponding elastic constant of a silicone light adjustable lens 120. In a CLA IOL 100, where the IOL 110 is considerably softer than the light adjustable lens 120, the “springiness” of the overall CLA IOL 100 can be considerably reduced relative to that of the light adjustable lens 120 alone. Such a CLA IOL 100 can be inserted with substantially improved control and predictability during cataract surgery, thus improving the surgical outcome.
As described in relation to
In some embodiments, the UV absorber can be related to the light adjustable lens 120.
In other designs, the UV absorber can be related to the IOL 110. Since the UV light needs to reach the light adjustable lens 120 for the adjustment procedure, in such embodiments the light adjustable lens 120 can be attached to the IOL 110 at a proximal surface of the IOL 110, so that the UV absorber in the IOL 110 does not block the UV illumination from reaching the light adjustable lens 120. With such an arrangement, in some embodiments, an ultraviolet absorbing material can be dispersed throughout the IOL 110; in others, the CLA IOL 100 can include the ultraviolet absorbing layer 130. This ultraviolet absorbing layer 130 can be on a proximal or on a distal surface of the IOL 110, since either of these designs still places the ultraviolet absorbing layer 130 distal to the light adjustable lens 120.
In embodiments of the composite light adjustable intraocular lens 100, the light adjustable lens 120 can be attached to the IOL 110 by a variety of designs. In some cases, the light adjustable lens 120 can be attached to the IOL 110 by a chemical reaction, a thermal treatment, an illumination treatment, a polymerization process, a molding step, a curing step, a lathing step, a cryo-lathing step, a mechanical process, an application of an adhesive, or by any combination of these methods.
(a) For example, CLA IOLs 100 with an attachment structure 135 can be modular. This can be advantageous for pre-operative purposes, as a surgeon may need to keep a much smaller inventory. Once pre-operative diagnostics determines what IOL 110 needs to be paired with what light adjustable lens 120, the surgeon can select a separately stored IOL 110, and a separately stored light adjustable lens 120, and assemble the CLA IOL 100 by inserting the two selected lenses into the attachment structure 135.
(b) The modularity can be advantageous post-operatively as well. If at the end of the cataract surgery it is determined that for whatever reason, the IOL 110 was not selected optimally, if a non-modular CLA IOL 100 was used, then the surgeon needs to reopen the eye and remove the entire implanted CLA IOL 100, including its extended haptics 114. Such a full-IOL removal can pose substantial challenges and can lead to undesirable medical outcomes, such as broken haptic pieces.
In contrast, if a modular CLA IOL 100 was implanted, then, upon the reopening of the eye the surgeon does not need to remove the entire CLA IOL. 100, only the non-optimal IOL 110, and exchange it with a better selected IOL 110. This procedure avoids the need to remove the entire CLA IOL 100, and thus reduces the risk of undesirable medical outcomes. Also, typically such replacement procedures may need a shorter incision, since only parts of the IOL are being replaced: another medical benefit.
(c) Finally, IOLs with taller structures have benefits in the context of reducing Posterior Capsule Opacification, or PCO. This will be described below in more detail in relation to
In embodiments of the CLA IOL 100, the IOL 110 can be an advanced and complex IOL, such as a multifocal IOL, an aspheric IOL, a toric IOL, or a diffractive IOL. Such advanced IOLs offer vision corrections beyond the correction of the optical power alone. They can help reducing presbyopia, astigmatism, cylinder, or other types of aberrations. However, the performance of these advanced IOLs requires the placement of the IOL with higher than usual precision. If the implanted IOL ends up misplaced, or misaligned, at the end of cataract surgery or later, the vision improvements and benefits can be substantially inferior relative to the outcomes promised to the patient. The fact that such unintended misalignments and rotations happen in a notable percent of cataract surgeries is a key factor limiting the wider market acceptance of such advanced IOLs.
In contrast, if a CLA IOL 100 gets misplaced, misaligned, or rotated relative to the planned location, angle, or direction in the eye, the light adjustable lens 120 of the CLA IOL 100 can be adjusted to compensate this misalignment, or rotation. Therefore, CLA IOLs 100 have the potential to deliver the promised vision improvements to the patients reliably. This benefit of the CLA IOLs 100 can start a fast expansion of the market acceptance and the market share of the advanced IOLs.
In some other embodiments, the insertion of the embodiments of
To compensate this unwanted medical outcome, the surgeon can early out a post-surgical diagnostic procedure to determine a corrective counter-rotating cylinder 216, the implementation of which can correct the unintended and unwanted rotation of the CLA IOL 100. As shown, the surgeon can perform a light adjustment procedure of the light adjustable lens 120 of the CLA IOL 100 in order to create the counter-rotating cylinder 216 in the light adjustable lens 120. The superposition of the implanted rotated cylinder 214 and the counter-rotating cylinder 216 can sum up into a shape of the light adjustable lens having a corrected cylinder 218, whose direction is aligned with the direction of the originally planned target cylinder 212. These steps are analogous to the steps of
In a demonstrative example, in an embodiment of the CLA IOL 100 that includes a toric IOL 110 for correcting a cylinder greater than 2D, the light adjustable lens 120 can be adapted to be able to correct a cylinder up to 2D. For example, if the toric IOL 110 was intended to correct a 6D cylinder, but the toric axis was rotated by 10 degrees, this translates into a 30% reduction of efficiency, as described earlier, providing a net 4D cylinder improvement for the patient. However, the surgeon can perform a light adjustment procedure on the light adjustable lens 120 to correct the 2D cylinder that was lost to the unintended rotation, thereby restoring the full 6D cylinder promised to the patient.
In the procedure described in relation to
Next,
Our brain learned to accept a limited degree of this chromatic aberration. Nevertheless, cataract surgery has the opportunity to provide an additional medical benefit by implanting chromatic aberration-compensating IOLs that compensate the eye's own chromatic aberration and image all wavelength components to the retina, thereby reducing the chromatic aberration and sharpening the vision.
The dependence of the index of refraction on the wavelength is often characterized by the Abbe number, defined as V=(n
With these introductory remarks, an intraocular lens can compensate chromatic aberrations, if the wavelength derivative of its optical power compensates the negative wavelength derivative of the eye optical power, so that ∂Pl/∂λ+∂Pe/∂Pe/∂λ≈0. In other words, ∂Pl/∂λ≈−∂Pe/∂λ>0.
Now, since regular (non-diffractive) intraocular lenses deliver a positive optical power Pl of about 20D, in the light of the introductory remarks, their ∂Pl/∂λ is negative, and thus they are unable to compensate the eye's own chromatic aberrations, because ∂Pe/∂λ is also negative.
However, embodiments of the CLA IOL 100 are made of two different lenses, the IOL 110, and the light adjustable lens 120. Such two-lens designs introduce a genuinely new possibility. One of the lenses of the CLA IOL 100 can have a negative optical power and thus a strongly positive ∂P/∂λ>0, so that the combined, two-lens CLA IOL 100 can compensate the chromatic aberration of the eye optical system, while the combined optical powers of the two lenses can still perform the primary function of the intraocular lens, to deliver an about constant 20D. In formulae, the first lens optical power Pl,1 and the second lens optical power Pl,2 of a two-lens CLA IOL 100 can simultaneously satisfy the following two relations:
P
l,1
+P
l,2=20D, (1)
∂Pl,1/∂λ+∂Pl,2/∂λ≈−∂Pe/∂λ>0 (2)
In some detail,
The magnitude of ∂n/∂λ, |∂n/∂λ| is relatively high for PMMA, while |∂n/∂λ| is typically low for silicone. Therefore, CLA IOLs 100 embodiments with the design of
P
IOL
+P
LAL≈20D, (3)
while at the same time the CLA IOL 100 is still capable of compensating the chromatic aberration of the eye:
∂PIOL/∂λ∂PLAL/∂λ≈-∂Pe/∂λ (4)
Such a CLA IOL 100 can deliver an overall optical power of about 20D, while the combined wavelength derivatives of the optical powers of the IOL 110 and the LAL 120 can largely compensate the chromatic aberrations of the eye optical system, thereby substantially reducing the overall chromatic aberration of the eye after the implantation of the CLA IOL 100. (Here, the “eye optical system” primarily refers to the cornea, as the crystalline lens has been removed by the cataract surgery.)
Accordingly, in embodiments of the CLA IOL 100, the IOL 110 has an IOL chromatic shift variation; the light adjustable lens 120 has a light adjustable lens chromatic shift variation; an eye, with a crystalline lens removed, has an eye chromatic shift variation; and a chromatic shift variation of the eye, with the composite light adjustable intraocular lens 100 implanted, can be less than a chromatic shift variation of the eye with the crystalline lens in place, wherein the chromatic shift variation is defined from a difference of a chromatic shift at 450 nm and at 650 nm.
In embodiments of the CLA IOL 100, an optical power of the IOL 110 can be negative; an optical power of the light adjustable lens 120 can be positive; and the chromatic shift variation of the eye, with the composite light adjustable intraocular lens implanted, can be less than 0.5D. In other embodiments, this chromatic shift variation can be less than 0.2D. In eyes with such achromator CLA IOLs 100 implanted, the blurriness of the image, caused by the chromatic dispersion, can be substantially smaller than that of the natural eye, thereby sharpening the vision in an additional aspect: a clear further medical benefit.
Ideas about achromator IOLs with related aspects has been proposed by E. J. Fernandez and P. Artal in an article entitled: “Achromatic doublet intraocular lens for full aberration correction”, at p. 2396, vol. 8 (2017) of the Biomedical Optics Express, the paper hereby being incorporated by reference in its entirety. While instructive in some aspects, this paper did not discuss, among others, aspects of light adjustability of the involved IOLs. Adapting the technology of this paper for light adjustable lenses involves further advanced concepts.
This enhanced force can have the following notable medical benefit. Posterior capsule opacification, PCO, is one of the well-known negative outcomes, or complications, of cataract surgery. PCO results from the growth and abnormal proliferation of lens epithelial cells (LECs) on the posterior capsule. Most PCOs are fibrous, or pearl-like, or a combination of both. Clinically, PCO can be detected as a wrinkling on the posterior capsule, for example. The development of PCO often involves three basic phenomena: proliferation, migration and differentiation of residual LECs.
While various pharmaceutical solutions have been developed to mitigate PCO, forming a sharp mechanical barrier in contact with the capsular bag 15 was also shown to reduce PCO. Such a barrier suppresses the fibrous growth and reduces LEC migration, thereby reducing PCO.
In embodiments of the CLA IOL 100, the sharp IOL edge 144 is pushed against the capsular bag 15 with unusually high force because the flint lens of the achromat has an unusually tall side 142 since it has negative optical power and thus its side is taller than its center. For this reason, achromat embodiments of the CLA IOL 100 exhibit the additional medical benefit of PCO reduction.
Yet another medical benefit of these CLA IOLs 100 with tall sides is that the higher pressing forces induce higher capsular bag tensions. This higher capsular tension tends to stabilize the location and the axis of the CLA IOL 100 better than the lower capsular tension induced by the flat regular IOLs, thereby preventing the CLA IOL 100 from tilting, or otherwise getting misaligned.
The taller IOL side 142 may necessitate the formation of a larger, or longer, surgical incision. This, in turn, may induce an unintentional astigmatism after the cataract surgery. However, since the light adjustable lens 120 can be adjusted after the surgery, in embodiments of the CLA IOL 100, this astigmatism can be compensated and eliminated efficiently by applying an astigmatism-compensating light adjustment procedure to the light adjustable lens 120.
The acrylic intraocular insert 110′ can include the intraocular lens (IOL) 110 with an optical power and can be thought of as an embodiment of the IOL 110. In some cases, the acrylic intraocular insert 110′ can include a carrier with approximately zero optical power. And in reverse, the intraocular lens (IOL) 110 can be thought of as an embodiment of the acrylic intraocular insert 110′, with, or without an optical power.
These embodiments include the adhesion promoter 300 to ensure that the two main constituents of the composite light adjustable IOL. 100, the acrylic intraocular insert 110′ and the silicone-based light adjustable lens 120 are chemically bonded together and do not peel apart after implantation and the light adjustment procedure.
Attaching an acrylic IOL to a silicone frame around its edges, or to a silicone biasing element by chemical means for presbyopic applications has been described before. However, there are at least the following differences between those IOLs and the presently described CLA IOL 100.
(1) The optical, or viewing, elements in those IOLs have unchanging, fixed shapes. Therefore, the strains and tensions at the acrylic-silicone joints can be minimized by a suitable fabrication process. Also, IOLs with underperforming joints can be discarded as part of the quality control during the fabrication process. This is in contrast to the embodiments of the CLA IOL. 100, where the light adjustment procedure changes the shape of the silicone-based light adjustable lens 120 after the implantation, while leaving the shape of the acrylic intraocular insert 100′ essentially unchanged, as illustrated in detail in
(2) In most of the previously described IOLs, the silicone forms a frame, or a biasing element, or is positioned around the edges of the acrylic IOL. In such IOLs, the silicone-acrylate interface is not within the optical path, and therefore there is not much of a requirement for the silicone-acrylic joint to not distort the imaging quality. In contrast, in embodiments of the CLA IOL 100, the silicone-acrylic interface is within the optical path, and thus the entire interface is expected to transmit light without distortion in spite of the light adjustment procedure inducing tensions and strains at the silicone-acrylic interface. The above two considerations illustrate marked differences between previous designs and embodiments of the CLA IOL 100.
Just like IOLs 110, embodiments of the acrylic intraocular insert 110′ can comprise at least one of a monomer, a macromer, an oligomer, and a polymer, selected from the group consisting of an acrylate, an alkyl acrylate, an aryl acrylate, a substituted aryl acrylate, a substituted alkyl acrylate, a halogen substituted acrylate, a halogen substituted methacrylate, an acrylic ester or acrylic acid, an acrylamide, a vinyl, and copolymers combining alkyl acrylates and aryl acrylates. For some CLA IOLs 100, the aforementioned monomers can be a methyl acrylate, an ethyl acrylate, an ethyl hexyl acrylate, a phenyl acrylate, an ethyl methacrylate, a trifluoroethyl acrylate, a trifluoroethyl methacrylate, an n-butyl acrylate, a hydroxy ethyl acrylate, a hydroxy methyl acrylate, an n-vinyl pyrrolidone, a phenoxyethyl acrylate, or polymers or co-polymers thereof.
Additionally, crosslinkers with corresponding his- or multi-functionality can be present to aid the polymerization. For some CLA IOLs 100, the crosslinker can be ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, propylene glycoldimethacrylate and propylene glycoldiethacrylate. Furthermore, the crosslinked network can be induced by thermal, UV-initiated, or catalyst-promoted reactions. For some CLA IOLs 100, thermal initiators can be 2,2-azobis(2,4-dimethylpentanitrile), 2,2-azobis(2,4-dimethylbutanenitrile), azobisisobutyro-nitrile, azobisisopropionitrile, or azobisisomethylpropionitrile. For some CLA IOLs 100, photo initiators can be benzophenones, benzoin alkyl ethers, benzil ketals, phosphine oxides, acyl oxime esters, acetophenones or acetophenone derivatives.
As described earlier in relation to
In addition, the CLA IOL 100 can include a photoinitiator, configured to be activated upon absorbing a refraction modulating illumination; and to initiate the stimulus-induced polymerization of the refraction modulating compound. To provide protection and safety. CLA IOLs 100 can include an ultraviolet absorber.
Next, embodiments of the adhesion promoter 300 will be described in detail. As mentioned above, the adhesion promoter 300 can contain the two orthogonal functional groups that can independently participate in polymerization using their unique chemistries: the first orthogonal functional group, configured to bond with an acrylic component of the acrylic intraocular insert 110′, and the second orthogonal functional group, configured to bond with a silicone component of the silicone-based light adjustable lens 120. In some embodiments of the CLA IOL 100, the adhesion promoter 300 can have structure (1) as follows.
wherein at least one of R3, R3′ and R3″ is a vinyl dialkylsiloxy pendant group with the structure (2)
the remaining of R3, R3′ and R3″ are independently selected from the group consisting of C1-C10 pendant alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl;
the first orthogonal functional group is the functional group to the left of R2;
the second orthogonal functional group is R6;
R1 is selected from the group consisting of a hydrogen, a monovalent hydrocarbon group, and a substituted C1-C12 alkyl, wherein the alkyl can be methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl;
R2 is an alkyl spacer with 1-10 carbon atoms, such as (—CH2)n, where n=1 through 10;
R4 and R5 are independently selected from the group consisting of C1-C10 pendant alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl; and
R6 is one of a vinyl group, a vinyloxy group, an allyl group, an allyloxy group, and a group with a carbon chain C1-C10.
In some embodiments of the CLA IOL 100, R1 is methyl, R2 is propyl, R3, R3′ and R3″ each is vinyl dialkylsiloxy, R4 and R5 each is a C1-10 alkyl chain, and R6 is vinyl.
In some embodiments, R2 can be a chain, in others, a branched, or a cyclic isomer of an alkyl spacer, such as cyclopentyl. Further, R2 can be a substituted vinyl aryl. Optionally, R2 may also have a substituted aromatic group such as a substituted phenyl or a substituted naphthyl.
The first orthogonal functional group to the left of R2 forms the covalent bond 322 with the acrylic intraocular insert 110′. The second orthogonal functional group is R6 that forms the covalent bond 320 with the silicone-based LAL 120 via the double bond interacting with silicone hydride to form a new covalent silicone carbon bond 320.
Adhesion promoters 300 with more double bonds form more covalent bonds 320 with the silicone-based LAL 120. The number of available double bonds can be increased by selecting
two or all three of R3, R3′ and R3″ to be a vinyl dialkylsiloxy pendant group, each containing an R6 with a double bond. The resulting adhesion promoter 300 is shown in structure (3).
This embodiment of the adhesion promoter 300 is called methacryloxypropyltris (vinyldimethylsiloxy)silane, with structure (3), where R1 is methyl, R2 is propyl, the R3, R3′ and R3″ are vinyldimethilsiloxy, R4 and R5 are methyl, and R6 is vinyl. This structure (3) is a suitable an adhesion promoter 300, since it contains 3 vinyl R6s, each with a double bond, and thus is capable of bonding to the silicone-based LAL 120 with multiplied strength, which is promising for preventing the peeling between the acrylic intraocular insert 110′ and the silicone-based LAL 120, and the optical distortions at their interface, as discussed above.
The overall strength of the adhesion between the acrylic intraocular insert 110′ and the silicone-based LAL 120, generated by the adhesion promoter 300 depends on the strength and number of the covalent bonds 320 per individual adhesion promoter molecule, as well as on the concentration of these molecules. It has been found that a concentration of the methacryloxypropyltris(vinyldimethylsiloxy)silane as adhesion promoter 300 above 5 weight % dispersed in the acrylic intraocular insert 110′ was sufficient (1) to prevent peeling between the acrylic intraocular insert 110′ and the silicone-based LAL 120 even after the refraction modulating illumination, and (2) to avoid the generation of optical distortions by the acrylic intraocular insert 110′ silicone-based LAL 120 interface. CLA IOLs 100 with a concentration above 10 weight % performed particularly well. For adhesion promoters 300 with structure (1) but where only one of the R3 groups was a vinyl dialkylsiloxy pendant group, a concentration higher than 10 weight % was found to provide sufficient quality bonding.
Structure (3) can be viewed as a monomer unit within the formulation of acrylic intraocular insert 110′, where it can act as an adhesion promoter 300. In related embodiments, the corresponding building block can be methacryloxypropyldi(vinyldimethylsiloxy)methylsilane, methacryloxypropyl(vinyldimethylsiloxy)dimethylsilane, acryloxypropyltris(vinyldimethylsiloxy)silane, methacryloxybutyltris(vinyldimethylsiloxy)silane, acryloxybutyltris(vinyldimethylsiloxy)silane, acryloxypropyldi(vinyldimethylsiloxy)methylsilane, methacryloxybutyldi(vinyldimethylsiloxy)methylsilane, acryloxybutyldi(vinyldimethylsiloxy)methylsilane, acryloxypropyl(vinyldimethylsiloxy)dimethylsilane, methacryloxybutyl(vinyldimethylsiloxy)dimethylsilane, acryloxybutyl(vinyldimethylsiloxy)dimethylsilane, styrylmethyltris(vinyldimethylsiloxy)silane, styrylethyltris(vinyldimethylsiloxy)silane, styrylmethyltrisdi(vinyldimethylsiloxy)silane, styrylethyldi(vinyldimethylsiloxy) methylsilane, styrylethyl(vinyldimethylsiloxy)dimethylsilane, and styrylethyl(vinyldimethylsiloxy)dimethylsilane, to name a few.
This unit can be coupled to the silicone-based LAL 120 by covalent bonds 320 between one or more silicon atoms of the silicone-based LAL 120 and one or more carbon atoms of the adhesion promoter 300, typically through its R6 group.
In some CLA IOLs 100, the covalent bonds are created via a hydrosilation reaction between the vinyl group of the vinyldialkylsiloxy group and an Si—H group of the silicone-based light adjustable lens 120. Adhesion promoters 300 with more branches (n>1) have more double bonded second orthogonal functional groups, and thus can provide stronger bonding to the silicone-based light adjustable lens 120, as mentioned in relation to structure (3) above.
In CLA IOLs 100, the silicone-based light adjustable lens 120 can be attached to the acrylic intraocular insert 110′ by at least one of a chemical reaction, a thermal treatment, an illumination treatment, a polymerization process, a molding step, a curing step, a lathing step, a cryo-lathing step, a mechanical process, an application of an adhesive, and by a combination thereof.
In some embodiments of the composite light adjustable IOL 100, the acrylic intraocular insert 110′ can be a toric acrylic intraocular insert 110′. This toric acrylic intraocular insert 110′ can have an optical power in some embodiments.
The description is closed by mentioning some additional advantages of composite light adjustable IOLs 100. (1) Composite light adjustable IOLs 100 can reduce the volume of the photopolymerizable materials relative to the silicone-only LALs, as the acrylic IOL 110, or acrylic, intraocular insert 110′, can provide a baseline optical power of 10D, 15D or even 20D. Thus, the silicone-based LAL 120 can be a much thinner layer that is used only for providing the change of the optical power relative to the baseline optical power of the acrylic IOL 110/insert 110′. The smaller volume of the photopolymerizable material translates to smaller intensity and radiance of the refraction modulating illumination, thereby further increasing the safety of the procedure.
(2) In some cases, the refraction modulating illumination has competing effects on the two surfaces of the silicone-based LAL 120. As illustrated in
A widely used, design for IOLs is to redirect the light by forming a diffractive pattern on a surface of the IOL, as mentioned before in relation to
A diffractive IOL 110 has a diffractive structure 350 that has a set of annuli, rings, or diffractive steps/zones 403i, where each ring supports a rising surface segment. The shape of these segments can be parabolical, sinusoidal or described by other functional forms. The height of the jumps at the boundaries between rings is chosen such that the difference of optical path lengths of light rays, propagating from neighboring segments, satisfies specific interference criteria at specified distances, such as at the focal distance.
However, all these diffractive IOLs 110 share the drawbacks of traditional IOLs as listed earlier, and have some additional problems on their own, as listed below. We start with presenting the known limitations of the existing IOL technologies, a list that includes limitations listed earlier. Limitations of existing acrylic diffractive IOLs include the followings.
L1. In a notable percent of cases the IOLs tend to shift and move away from their optimal position after implantation. However, existing IOLs cannot be adjusted after implantation to compensate for these shifts, and thus, in spite of their premium pricing, do not deliver optimal outcomes.
L2. The lack of adjustability necessitates extensive diagnostic examinations using expensive diagnostic equipment prior to surgery, and even that does not guarantee optimal outcomes.
L3. Toric IOLs are particularly sensitive to post-operative rotations induced by tissue healing. For toric IOLs, an unintended rotation of the toric IOL axis by only 10 degrees after implantation can cause about 30% loss of visual acuity.
L4. For diffractive IOLs patients report undesirable photic phenomena: blurred vision, glare, halos, dysphotopsia. These are created by the sharp edges of the pattern of the diffractive structure getting rounded, e.g., by chemical reactions such as oxidation. These can be further exacerbated by residual refractive error. These problems often necessitate performing a subsequent LASIK procedure after cataract surgery, or even an IOL explant. Such a second surgery has additional risks, such as corneal ectasia, and persistent dry eye.
All these limitations L1-L4 of diffractive acrylic IOLs can be reduced and mitigated if the diffractive IOL is combined with an adjustable LAL. Embodiments of such composite light adjustable IOLs 100, or CLA IOLs 100, will be described from here on, starting with the listing of their benefits as follow s.
B1. A CLA IOL 100 is adjustable. Therefore, an adjustment by illumination after the cataract surgery can correct any post-surgical tilt, shift, rotation and movement of the IOL, thereby guaranteeing an essentially optimal outcome.
B2. The adjustability of a CLA IOL 100 reduces, and often eliminates the necessity of expensive and extensive diagnostic pre-surgical examinations, because patient dissatisfaction with the outcome of the surgery can be corrected after the surgery with a light adjustment of the CLA IOL 100.
B3. The toric prescription can be induced by irradiation after the implantation of a CLA IOL 100. The direction and magnitude of this post-surgically induced toricity will be aligned and set by the prescription with excellent precision. This feature also simplifies manufacturing and inventory, since presently often 5-10 diffractive IOLs of the same sphere prescription have to be supplied by the manufacturer and stored by the ophthalmologist to cover all possible toric prescriptions. It is noted that some of the toric prescriptions can be implemented in the acrylic diffractive IOL to extend the range of correction of the higher levels of astigmatism, which are less sensitive to prediction errors of axis.
Remarkably and encouragingly, combining specifically acrylic diffractive IOLs 110 with LALs 120 mitigates some of the challenges of the LAL technology, including the following.
B4. Silicone-based LALs are stiffer than acrylate IOLs, and therefore often appear more “springy” in comparison. One consequence of this springiness is that, during the LAL implantation process, the folded LALs unfold quite fast as they are pushed out from the surgical inserter handpiece into the eye. This quick unfolding of the silicone-based LALs can make the control of the insertion and the proper alignment of the LALs somewhat challenging for a surgeon during surgery. In contrast, acrylate-based IOLs have softer elastic constants and more favorable viscoelastic character; and thus unfold slower during the insertion. This aspect allows the surgeon to exercise more control over the insertion of acrylate IOLs. Thus, acrylic CLA IOLs 100 are less “springy” and unfold more smoothly.
B5. Some existing LALs are three-piece: the two haptics are often separately fabricated and subsequently inserted into the central lens body. This design feature increases manufacturing costs, may lead to a higher rate of haptics misalignment during manufacture, and to separation of the haptics from the LAL lens body during the insertion. In contrast, some acrylate-based TOLs mitigate these challenges by having a one-piece design, where integrated haptics are formed from the same lens material and with the same molding step as the central lens body of the IOL. Such one-piece designs have lower manufacturing costs, deliver good haptics alignment with the lens body, and reduce the risk of haptic separation from the lens body during insertion. CLA TOLs 100 with a one-piece design acrylic diffractive IOL 110, with their haptics molded from the acrylic itself, can achieve all these benefits.
Further benefits are associated with a particular CLA IOL design, where the LAL 120 is proximal/frontal/anterior, and the acrylic diffractive IOL 110 is posterior.
B6. As described above, the LAL technology protects the retina from UV exposure by employing the UV absorbing layer 130 formed posterior to the LAL 120. Manufacturing this UV absorbing layer 130 involves an additional manufacturing step with its own challenges. CLA IOLs can eliminate the need for forming the separate UV blocking layer 130 by dispersing the same UV blocking material in the acrylic diffractive IOL 110 itself.
B7. Silicone LALs 120 can be contraindicated in patients who likely would need retinal vitrectomy surgery since it tends to be difficult to visualize retinal troughs during surgery if air or silicone oil is inserted into vitreous cavity. However, CLA IOLs 100 that have the acrylic diffractive IOL 110 placed on the posterior surface of the silicone LAL 120 block contact of the silicone LAL 120 with air or silicone oil during any potential subsequent retinal procedures and thus can overcome this contraindication.
B8. As shown, e.g. in
B9. The suppression of the intermediate diffractive peak in the Panoptix IOLs is based on the negative interference of the diffracted rays corresponding to a particular diffraction order, and is thus particularly sensitive to the sharpness and precise shape of the diffractive structure 350. Therefore, it is particularly beneficial to attach a Panoptix-type, suppressed-diffractive-order IOL to the posterior side of a LAL 120 that bends much less than the anterior side.
B10. The edges of the diffractive structure 350 are formed via a delicate trade-off Making the edges sharp minimizes wavefront error, but enhances scattering at off-design wavelengths. On the other hand, making the edges round increases wavefront error, but reduces the scattering. Therefore, the optimal rounding of the edges is delicately selected during the design of such diffractive IOLs. CLA IOLs 100, where the diffractive IOL 110 is posterior to the LAL 120 and has its diffractive structure 350 at the interface of these lenses, as shown in
The above-listed benefits B1-B10 articulate numerous advantages and benefits of CLA IOLs 100 that include a front/anterior silicone LAL 120 and a back/posterior acrylic diffractive IOL 110, Considerations presented in relation to
As discussed before,
Finally,
of 60 cm; or close to the distant focal point 404d, such as to 120 cm.
In some CLA IOLs 100 at least one of a monomer, a macromer, and a polymer of the acrylic diffractive intraocular lens 110 is having at least one functional group, wherein the functional group includes at least one of hydroxy, amino, and vinyl, mercapto, isocyanate, carboxyl, hydride, and is one of cationic, anionic and neutral.
In some CLA IOLs 100 the silicone light adjustable lens 120 includes a first polymer matrix; and a refraction modulating composition, dispersed in the first polymer matrix; wherein the refraction modulating composition is capable of stimulus-induced polymerization that modulates a refraction of the silicone light adjustable lens 120. The first polymer matrix can include a siloxane-based polymer, formed from macromer and monomer building blocks with at least one of an alkyl group and an aryl group.
In some CLA IOLs 100, the silicone light adjustable lens 120 can include a photoinitiator, to absorb a refraction modulating illumination; to be activated upon the absorption of the illumination; and to initiate the polymerization of the refraction modulating compound. The silicone light adjustable lens 120 can further include at least one of an ultraviolet-absorber dispersed throughout; and an ultraviolet absorbing layer at a distal surface of the silicone light adjustable lens 120, like the UV absorbing layer 130 of
In other embodiments of the CLA IOL 100, the acrylic diffractive IOL 110 can include at least one of an ultraviolet-absorber dispersed throughout; and an ultraviolet absorbing layer at a distal surface of the acrylic diffractive IOL 110.
wherein Ai is a corresponding step height relative to a base curvature of the acrylic diffractive intraocular lens 110, yi is the height relative to an X-axis in a corresponding segment, ϕi is a relative phase delay from the x-axis, and xi is the position of the diffractive step 403i along the x-axis. The panel tables in
In some composite light adjustable intraocular lens CLA IOL 100, the acrylic diffractive IOL 110 has an anterior surface and a posterior surface; and the diffractive structure 350 is disposed on at least one of the anterior surface and the posterior surface. As shown in FIG. 22B and
In some of these CLA IOLs 100 the plurality of annular diffractive steps 403i are configured such that a diffraction efficiency of the lowest diffractive order for a 3 mm aperture is at least 40%; a diffraction efficiency of the highest diffractive order for the 3 mm aperture is at least 20%; and a diffraction efficiency of each of the near-intermediate diffractive order and the far-intermediate diffractive order for the 3 mm aperture is in the range of 10-20%. As such, in these CLA IOLs 100 the suppression of one of the diffractive orders down to the range of 10-20% is less than in previously described embodiments, where one of the intermediate orders had a diffraction efficiency suppressed below 10%.
In yet other embodiments of the CLA IOLs 100, the diffractive structure 350 includes a plurality of annular diffractive steps 403i and four consecutive diffractive orders; wherein the composite light adjustable intraocular lens 100 produces a near focal point 404n, an intermediate focal point 404i, and a distance focal point 404d, each corresponding to a different one of the four consecutive diffractive orders; and the plurality of annular diffractive steps 403i of the diffractive structure 350 are configured such that one of the four diffractive orders is suppressed and at least a portion of the energy associated with that suppressed diffractive order is redistributed to one of the near focal point 404n, the intermediate focal point 404i, and the distance focal point 404d. In some CLA IOLs 100, the four consecutive diffractive orders include a lowest diffractive order, a highest diffractive order, and two intermediate diffractive orders; and the suppressed diffractive order is one of the two intermediate diffractive orders.
In embodiments, the adhesion promoter 300 has the structure
wherein at least one of R3, R3′ and R3″ is a vinyl dialkylsiloxy pendant group with the structure
the remaining of R3, R3′ and R3″ are independently selected from the group consisting of C1-C10 pendant alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl; the first orthogonal functional group is the functional group to the left of R2; the second orthogonal functional group is R6; R1 is selected from the group consisting of a hydrogen, a monovalent hydrocarbon group, and a substituted C1-C12 alkyl, wherein the alkyl can be methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl; R2 is an alkyl spacer with 1-10 carbon atoms, such as (—CH2)n, where n=1 through 10; R4 and R5 are independently selected from the group consisting of C1-C10 pendant alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, sec-butyl, t-butyl, cyclobutyl, or methylcyclopropyl; and R6 is one of a vinyl group, a vinyloxy group, an allyl group, an allyloxy group, and a group with a carbon chain C1-C10.
In some CLA IDLs 100, the acrylic diffractive intraocular lens 110 is a toric acrylic diffractive intraocular lens 110.
While this document contains many specifics, details and numerical ranges, these should not be construed as limitations of the scope of the invention and of the claims, but, rather, as descriptions of features specific to particular embodiments of the invention. Certain features that are described in this document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to another subcombination or a variation of a subcombinations.
This application is a continuation-in-part of co-pending patent application U.S. Ser. No. 16/849,556, entitled: “Composite Light Adjustable Intraocular Lens with Adhesion Promoter”, by I. Goldshleger, J. Kondis, R. M. Kurtz, and R. Shrestha, filed on Apr. 15, 2020, which is a continuation-in-part of patent application U.S. Ser. No. 15/607,681, entitled: “Composite Light Adjustable Intraocular Lens”, by I. Goldshleger, J. Kondis, R. M. Kurtz, R. Shrestha, and G. Zimanyi; filed on May 29, 2017, both applications incorporated herein by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16849556 | Apr 2020 | US |
| Child | 17180790 | US | |
| Parent | 15607681 | May 2017 | US |
| Child | 16849556 | US |
