Photoaccommodating intraocular lens with a modulating absorbing front protective layer

Abstract

An embodiment of a modulating absorbing light regulating lens (MALAL) includes a light regulating lens comprising a light-modifiable material that can change its optical properties upon modulating illumination, and a modulating absorbing front protective layer comprising a modulating absorbing compound having absorption properties that can be modulated by a modulating stimulus. Another embodiment includes a method of modulating the optical properties of a modulating absorbing light regulating lens, comprising: reducing absorption of a modulating absorbing compound in a modulating absorbing front protective layer of a MALAL previously implanted in an eye with a modulating stimulus; and changing the optical properties of the MALAL light regulating lens by applying modulating illumination.

Description

[Technical Field]

[0001] The present invention relates to light accommodating lenses, and more particularly to light accommodating lenses with modulable absorption. [Background technology]

[0002] Cataract surgery techniques and tools continue to undergo impressive advancements. Next-generation phacoemulsification platforms and newly invented surgical lasers continue to improve intraocular lens (IOL) placement accuracy and reduce adverse medical outcomes. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] U.S. Patent No. 8,604,098 [Patent Document 2] U.S. Patent No. 8,933,143 [Patent Document 3] U.S. Patent No. 6,905,641 Summary of the Invention [Problem to be solved by the invention]

[0004] However, even with carefully planned IOL selection and implantation into the capsular bag using precise surgical instruments, healing and scarring of ocular tissues after implantation often causes the IOL to migrate or tilt from its optimally planned position within the eye's capsular bag. This settling process can take several weeks. This migration and tilt can compromise the optical performance of the IOL and, therefore, the overall medical outcome of cataract surgery.

[0005] Recently, photoaccommodating intraocular lenses (LALs) have been invented and developed to address this issue. Like conventional IOLs, LALs can undergo migration and tilt during the settling process, which takes several weeks after implantation into the capsular bag. However, LAL migration or tilt can be corrected by adjusting the optical properties of the implanted LAL. This adjustment can be achieved by illuminating the LAL with an ultraviolet (UV) beam with a carefully selected spatial profile.

[0006] To prevent the UV portion of sunlight from altering the optical properties of the LAL in the weeks between implantation and the photoaccommodation procedure, patients are asked to follow instructions to wear UV-blocking eyewear. However, even minor noncompliance, such as a patient forgetting to wear UV-blocking sunglasses while out for a walk on a sunny day, can result in uncontrolled and undesirable changes to the optical properties of the LAL. U.S. Patent Nos. 8,604,098 and 8,933,143, both of which are entitled "On-demand photoinitiated polymerization" and issued to Boydston et al., propose the introduction of a "masking compound" to address this issue. However, as discussed below, these designs do not address the issue of unintentional lens modification caused by patient noncompliance. Therefore, there remains an unmet medical need for improved photoaccommodating lens technology that reduces and potentially eliminates the need for strict patient compliance with wearing UV-blocking eyewear. [Means for solving the problem]

[0007] The above-mentioned needs are addressed by embodiments of a Modulatable Absorbent Light Modulating Lens (MALAL) that includes a light modulating lens that includes a photo-modifiable material, capable of changing optical properties upon modulating illumination, and a modulatable absorbing front protective layer that includes a modulatable absorbing compound having absorption properties that can be modulated by a modulating stimulus.

[0008] Other embodiments include a method for adjusting the optical properties of a modulatable absorbing light regulating lens, comprising the steps of reducing the absorption of a modulatable absorbing compound in a modulatable absorbing front protective layer of a MALAL previously implanted in the eye with a modulating stimulus, and changing the optical properties of the MALAL light regulating lens by applying modulating illumination. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a diagram showing a light-adjusting lens 10. FIG. [Figure 2] FIG. 1 illustrates the formation of zones with altered optical properties due to excessive UV irradiation. [Figure 3A] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 3B] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 3C] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 3D] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 3E] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 3F] 1 illustrates an embodiment of a Modulatory Absorbing Light Modulating Lens (MALAL) 100. FIG. [Figure 4] FIG. 1 illustrates the chemical nature of the photo-modifiable material 111. [Figure 5A-C] FIG. 10 is a diagram showing the light adjustment steps of MALAL100. [Figure 5D-F] FIG. 10 is a diagram showing the light adjustment steps of MALAL100. [Figure 6] FIG. 10 illustrates the absorption of single source illumination in the anterior protective layer 120 and LAL 110 during treatment. [Figure 7A] 3A-3C illustrate various ways in which a modulatable absorbing compound 300 can be associated with a polymer host matrix 112. [Figure 7B]3A-3C illustrate various ways in which a modulatable absorbing compound 300 can be associated with a polymer host matrix 112. [Figure 7C] 3A-3C illustrate various ways in which a modulatable absorbing compound 300 can be associated with a polymer host matrix 112. [Figure 7D] 3A-3C illustrate various ways in which a modulatable absorbing compound 300 can be associated with a polymer host matrix 112. [Figure 8A] FIG. 1 shows the chemical composition of azobenzene. [Figure 8B] FIG. 1 shows the absorption spectrum of azobenzene. [Figure 9] FIG. 1 shows the chemical composition and absorption spectrum of the trans-type photoisomer of vinylphenylazopyrazole. [Figure 10A] FIG. 1 shows the chemical composition and absorption spectrum of 4-aminoazobenzene. [Figure 10B] FIG. 1 shows the chemical composition and absorption spectrum of 4-(4′-hydroxyphenylazobenzoic acid). [Figure 11] FIG. 1 shows the time evolution of the extinction coefficient during the trans-cis transition. [Figure 12A] FIG. 1 shows the time evolution of the extinction coefficient during the trans-cis transition over an extended wavelength range in the visible spectrum. [Figure 12B] FIG. 1 shows the time evolution of the extinction coefficient during the trans-cis transition over an extended wavelength range in the visible spectrum. [Figure 13] FIG. 1 illustrates the reversibility of absorption modulation. [Figure 14A] FIG. 1 illustrates the possible, but highly unlikely, formation of small zones in MALAL 100. [Figure 14B] FIG. 1 illustrates the possible, but highly unlikely, formation of small zones in MALAL 100. [Figure 14C] FIG. 1 illustrates the possible, but highly unlikely, formation of small zones in MALAL 100. [Figure 15A]1A-1C illustrate steps in a method for adjusting the optical properties of a modulatable absorbing light-tuning lens. [Figure 15B] 1A-1C illustrate steps in a method for adjusting the optical properties of a modulatable absorbing light-tuning lens. DETAILED DESCRIPTION OF THE INVENTION

[0010] This document describes embodiments of photoaccommodating intraocular lenses that provide improvements related to the medical needs identified above. This description begins by reviewing photoaccommodating lens technology in some detail.

[0011] FIG. 1 illustrates a light accommodating lens (LAL) 10 that can be stabilized within the capsular bag by haptics 12 during implantation. As discussed above, the LAL 10 can shift or tilt away from its optimal, planned position within the capsular bag within the first few weeks after cataract surgery due to scarring and healing of ocular tissues. Corneal healing can also significantly impact the resulting refraction. A key innovation in LAL technology is determining how to adjust the optical properties of the LAL 10 to compensate for this unplanned shift or tilt after the LAL 10 is secured in the capsular bag. This determination can involve objective measurements and subjective patient feedback. The LAL 10 is then illuminated with ultraviolet (UV) light having a spatial profile or nomogram selected to induce adjustments in the optical properties of the LAL to compensate for the determined shift or tilt.

[0012] Given that the optical properties of LAL10 are sensitive to UV light, patients are instructed to wear UV-blocking eyewear in the weeks between implantation and adjustment to prevent the UV portion of solar radiation from inadvertently modifying the optical properties of LAL10. However, even slight non-compliance, such as a patient forgetting to wear UV-blocking eyewear when going out, can result in significant changes to the optical properties of LAL10.

[0013] The consequences of such non-compliance are shown in some detail in Figure 2 through a cross-section of LAL10 after exposure to significant incident UV illumination. UV illumination photopolymerizes zone 20 of LAL10 to a significant spatial extent, thus modifying the optical properties of LAL10 to a significant and uncontrolled extent, thus worsening the visual outcome.

[0014] 3A-3F illustrate an embodiment of a modulating absorbing light regulating lens (MALAL) 100 suitable for preventing the formation of such undesirable zones in the event of accidental non-compliance. The MALAL 100 of FIG. 3A includes a light regulating lens LAL 110 capable of changing its optical properties upon modulating illumination, which can include a light-modifiable material 111 and a modulating absorbing front protective layer 120 including a modulating absorbing compound 300 having absorption properties that can be modulated by a modulating stimulus. The optical properties of the LAL 110 can be tuned by adjusting the shape of the LAL 110, the refractive properties, refractive index, absorption properties, or polarization properties of the LAL 110, or a combination of these properties of the LAL 110, thereby changing the optical properties of the MALAL 100. The MALAL 100 can further include haptics 130, typically extending from the light regulating lens 110. Embodiments of the haptics 130 can include one, two, three, or more individual arms extending from the LAL 110. In other embodiments, the haptics can be flat, flexible extensions of the LAL 110 having a rectangular or modified rounded rectangular design. In some embodiments, the haptics 130 can extend from the modulated absorbing front protective layer 120 or support structures.

[0015] To put the description of MALAL 100 into context, we first provide a little more detail on the light accommodating lens LAL 110 itself in Figures 4 and 5A-5F.

[0016] 4 shows that the photomodifiable material 111 within the LAL 110 of the MALAL 100 can include a polymer host matrix 112. The polymer host matrix 112 can be a silicone-based matrix, an acrylate-based matrix, a collamer, a hybrid silicone-acrylate-based matrix, or a multilayer matrix combining at least two of these matrices.

[0017] In the LAL 110 of the MALAL 100, the photomodifiable material 111 can further include photopolymerizable monomers or macromers 113 capable of photoinduced polymerization. These photopolymerizable monomers / macromer 113 can further include photopolymerizable endgroups 114. The photomodifiable material 111 can also include a photoinitiator 115, which can be separate from the photopolymerizable monomers / macromer 113 or can be a terminal functional group of the photopolymerizable monomers / macromer 113.

[0018] A modulating stimulus, such as UV illumination as described above, can activate the photoinitiator 115, which can further induce photopolymerization of the photopolymerizable monomer / macromer 113, typically via the photopolymerizable end groups 114 of the photopolymerizable monomer / macromer 113. As described below, this photopolymerization process tunes the optical properties of the LAL 110 and, therefore, the MALAL 100.

[0019] The LAL 110 of the MALAL 100 can further include a dispersed ultraviolet (UV) absorber 116. This UV absorber 116 can serve different roles. One of these roles is to ensure that essentially all incident UV illumination is safely absorbed within the LAL 110, thereby providing retinal safety for the eye. Additionally, the UV absorber 116 can also serve to control and shape the spatially varying depth profile of the MALAL 100.

[0020] Thus far, embodiments of the MAL 110 have been described that are tunable with UV illumination as the conditioned illumination. In other embodiments, the conditioned illumination can include other portions of the electromagnetic spectrum, such as specific portions of the UV spectrum or the infrared portion. The conditioned illumination can also be incoherent or coherent laser-like illumination that can be applied simultaneously or sequentially to large areas of the MAL 110 in a scanning manner.

[0021] FIGS. 5A-5F illustrate in some detail the process of tailoring the optical properties of the LAL 110 of the LAL 100. FIG. 5A shows that the first step in the LAL technique is the traditional implantation of the LAL 110 into the eye of a cataract patient. FIG. 5B shows that the implanted LAL 110 can include a photopolymerizable monomer / macromer 113 embedded in a polymer host matrix 112. The LAL 110 often shifts and tilts within the lens capsule over the weeks following implantation, and as noted above, corneal healing also affects the optical properties of the eye. Once the LAL 110 has settled within the lens capsule after several weeks, the optical properties of the LAL 110 can be adjusted by applying conditioning illumination 210 to optically compensate for this shift, tilt, and the optical consequences of corneal healing. The conditioning illumination 210 is applied with a spatial profile, sometimes referred to as a nomogram, designed to induce adjustments to the optical properties of the LAL 110 to compensate for the shift and tilt of the LAL 110. In some embodiments, the conditioned illumination 210 may be generated by a UV source, such as a mercury lamp or a UV LED. A desired spatial profile may be achieved by deflecting or modulating the generated conditioned illumination 210 with a digital mirror device or suitable alternative.

[0022] FIG. 5C shows that tailored irradiation 210 can polymerize spatially varying portions of photopolymerizable monomer / macromer 113 (shown in bold) into photopolymerizable macromer 113p with a predetermined spatial profile.

[0023] FIG. 5D shows that the spatially varying density of the induced polymerized macromers 113p induces a spatially varying density of the remaining unpolymerized monomers / macromer 113. This creates a spatially varying chemical potential that causes the unpolymerized monomers / macromer 113 to diffuse into the central region of the LAL 110. This diffusion causes the central region of the LAL 110 to expand, thus increasing the optical power of the LAL 110 and generating a hyperopic adjustment. The embodiments described above adjust the optical properties of the LAL 110 by adjusting the shape of the LAL 110. For some classes of photomodifiable material 111, the conditioning irradiation 210 can adjust the optical properties of the LAL 110 in other ways, such as by adjusting the refractive index of the photomodifiable material 111. Finally, in some embodiments, both the shape and refractive index of the photomodifiable material 111 can be adjusted by the conditioning irradiation 210. Furthermore, if a myopic adjustment, i.e., a reduction in the optical power of the LAL 110, is desired, the profile of the conditioning irradiation, and therefore the induced polymerization, can be concentrated at the periphery of the LAL 110 rather than at its center.

[0024] FIG. 5E illustrates the fact that photopolymerizable monomers / macromers 113 that were not polymerized by the conditioning irradiation 210 remain after the conditioning irradiation 210 and may subsequently polymerize when UV-containing ambient light reaches the LAL 110. Such subsequent polymerization further uncontrollably and undesirably alters the optical properties of the LAL 110. The LAL technique addresses this issue by applying lock-in irradiation 220 to the LAL 110 some time after the conditioning irradiation 210 to polymerize essentially all of the remaining photopolymerizable monomers / macromers 113. Typically, this lock-in irradiation 220 is power neutral, as shown in FIG. 5F, i.e., it is not intended to further condition the optical properties of the LAL 110. In some cases, if for some reason the conditioning process of FIG. 5B does not result in the expected optical results, non-power-neutral lock-in irradiation 220 can be applied. After essentially all of the macromers 113 have been polymerized by the lock-in irradiation 220, subsequent exposure to sunlight or ambient light cannot induce further polymerization and further change the optical properties of the LAL 110. Thus, the steps described in Figures 5A-5AF constitute an LAL technique that can provide optimal, predetermined optical results despite potential LAL migration and tilt, and post-implant corneal healing. This LAL adjustment process described in connection with Figures 5A-5F is described in further detail in commonly assigned U.S. Patent No. 6,905,641 to Platt et al., entitled "Delivery System for Post-Operate Power Adjustment of Adjustable Lens," which is incorporated herein by reference in its entirety.

[0025] As mentioned above, the patient is instructed to wear UV-blocking glasses throughout the steps of Figures 5A-5E until all of the photopolymerizable macromer 113 has been photopolymerized by the conditioning exposure 210 and lock-in exposure 220 to prevent unintended changes to the optical properties of the LAL 110. However, this requirement over an extended period of several weeks can be inconvenient for patients who may inadvertently fail to comply, thereby causing undesired optical changes to the LAL 110. Embodiments of the MALAL 100 provide an improved technique to ensure that the optical properties of the LAL 110 remain under control when included in the MALAL 100, even if the patient fails to comply, such as by forgetting to wear the UV-blocking glasses.

[0026] Referring again to FIG. 3A , the MALAL 100 further includes a modulatable absorbing front protective layer 120 positioned forward relative to the LAL 110, which includes a modulatable absorbing compound 300 having absorption properties that can be modulated by a modulation stimulus 310. The modulatable absorbing compound 300 can have a high-absorption conformation and a low-absorption conformation, and the modulatable absorbing compound 300 can transition from a high-absorption conformation to a low-absorption conformation upon absorption of a high-to-low modulation stimulus 310-htl. Furthermore, the modulatable absorbing compound 300 can transition from a low-to-high absorption conformation upon absorption of a low-to-high modulation stimulus 310-lth. To avoid confusion, the high-to-low modulation stimulus 310-htl and the low-to-high modulation stimulus 310-lth can both be simply referred to as the modulation stimulus 310, even though they are generated by different sources. Furthermore, modulated absorption compound 300 in a high absorption conformation may be referred to as high absorption isomer 300-h, while modulated absorption compound 300 in a low absorption conformation may be referred to as low absorption isomer 300-l. In still other cases, modulated absorption compound 300 may be referred to as a chromophore, with its high absorption conformation referred to as high absorption chromophore 300-h and its low absorption conformation referred to as low absorption chromophore 300-l.

[0027] When such a MALAL100 is used in the LAL technology of Figures 5A-5F, the MALAL100 can be fabricated and implanted intraocularly with the modulated-absorbing compounds 300 of the modulated-absorbing front protective layer 120 in a highly absorbing conformation. This fabrication method provides the modulated-absorbing front protective layer 120 with strong protection for the photo-modifiable material 111 of the LAL110 against accidental UV exposure in the weeks between the steps of Figures 5A and 5B, potentially caused by non-compliance such as forgetting to wear UV-blocking glasses. In this section and beyond, the photo-modulation procedure is described with reference to the steps shown in Figures 5A-5F, where the LAL110 is intended to be the LAL110 in an embodiment of the MALAL100.

[0028] Some embodiments of the MALAL 100 can provide more than just protection from accidental non-compliance. Some MALALs 100 can be manufactured to provide sufficiently strong protection that even wearing UV-blocking glasses is unnecessary between implantation and lock-in of the MALAL 100. This MALAL 100 benefit is a great relief to patients and physicians because it enhances patient comfort and essentially eliminates the risk of unintentional non-compliance and its undesirable consequences. In these MALALs 100, by selecting a modulatable absorbing compound 300 with sufficiently high UV absorption and a modulatable absorbing front protective layer 120 with a sufficient thickness, these factors combine to sufficiently protect the photomodifiable material 111 of the LAL 110 from solar UV radiation during the several weeks from implantation in FIG. 5A through the conditioning procedure in FIG. 5B and lock-in in FIG. 5E, so that the optical properties of the MALAL 100 do not change despite exposure to solar UV radiation.

[0029] Once the MALAL 100 has settled within the lens capsule, it is time to adjust the optical properties of the LAL 110 of the MALAL 100, as already outlined in FIG. 5B. This procedure, in addition to the usual LAL techniques, begins by first applying a high-low modulation stimulus 310-htl to cause the modulo-absorbing compound 300 to transition from a high-absorbing isomer 300-h to a low-absorbing isomer 300-l. Before this transition, the conditioning radiation 210 could not pass through the high-absorbing isomer 300-h of the modulo-absorbing front protective layer 120; after this transition to the low-absorbing isomer 300-l, the conditioning radiation 210 can pass through the modulo-absorbing front protective layer 120 to reach the LAL 110, thereby adjusting its optical properties.

[0030] 6, in some embodiments, the source of the modulation stimulus 310 can be the same as the source of the conditioning illumination 210, such as a mercury lamp or UV LED. In such a single shared source embodiment, the MALAL 100 can be illuminated by a UV beam from the shared source that initially serves as the dominant high-low modulation stimulus 310-htl, but as illumination transitions the modulating absorbing compound 300 in the front protective layer 120 from a high absorbing isomer 300-h to a low absorbing isomer 300-l, an increasing proportion of the UV beam passes through the front protective layer 120 to reach the LAL 110, thus increasingly serving as the dominant conditioning illumination 210, as shown. In some embodiments, the spatially varying profile of illumination from the shared source can change over time. During the initial period when the illumination is predominantly the modulated stimulus 310, the spatial profile can be selected to be flat-top, largely independent of radius, to avoid adjusting the optical power of the LAL 110, while at a later time when the illumination is predominantly the modulated irradiance 210, the spatially varying profile can be switched to a scaled profile, such as a polynomial or Gaussian truncated at a large radius, as needed. In other embodiments, the spatially varying profile can be scaled throughout the illumination time. Finally, in yet other embodiments, the illumination can be applied with a flat-top profile while predominantly the modulated stimulus 310, then stopped, and then resumed with a scaled profile for the time interval when the illumination is predominantly the modulated irradiance 210.

[0031] Thus far, embodiments of MALAL100 have been described as being tunable by UV illumination as the modulation stimulus 310, however, in other embodiments, the modulation stimulus 310 can take other forms including electromagnetic illumination, laser illumination, infrared illumination, ultraviolet illumination, magnetic stimulation, electric field, chemical stimulation, heat transfer, energy transfer, ultrasound-mediated stimulation, mechanical stimulation, thermal stimulation, or thermal relaxation.

[0032] 3A-3F illustrate that the front protective layer 120 can be positioned in several different ways in front of the LAL 110. In the embodiment of FIG. 3A, a modulating absorbing compound 300 can be dispersed within the front surface region 122 of the light regulating lens LAL 110 to form the modulating absorbing front protective layer 120.

[0033] 7A-7D show that modulating absorbing compound 300 can be localized in polymer host matrix 112 in the anterior region 122 of light regulating lens 110 in a variety of ways. Figure 7A shows that modulating absorbing compound 300 can be localized in polymer host matrix 112 by one or more bonds 302 to crosslinkers 117 of polymer host matrix 112, or by chains 303 in the polymer host matrix as shown in Figure 7B. In such embodiments, the one or more chemical bonds 302 localizing modulating absorbing compound 300 can include chemical bonds connecting carbon or silicon to carbon, silicon, oxygen, nitrogen, hydrogen, sulfur, or halogen atoms.

[0034] Figure 7C shows that in some embodiments, the modulating absorbing compound 300 can be mobile relative to the polymer host matrix 112, or can be a long-chain polymer that interpenetrates the photomodifiable material 111. Finally, Figure 7D shows that the modulating absorbing compound 300 can be bound to an interpenetrating network 118 entangled in the polymer host matrix 112. The more mobile the modulating absorbing compound 300 is relative to the polymer host matrix 112, the more likely it will require an isolation layer to prevent the modulating absorbing compound 300 from diffusing into the eye itself or into the LAL 110.

[0035] 3B shows that in other embodiments of the MALAL 100, the modulating absorbing front protective layer 120 can be a layer adhered to or deposited on the front surface region 122 of the light regulating lens LAL 110. In these embodiments, the modulating absorbing compound 300 is less likely to exhibit diffusion into the LAL 110.

[0036] 3C illustrates that in some MALALs 100, the modulating absorbing front protective layer 120 can be positioned at least partially separate from the front surface of the light regulating lens LAL 110. Such embodiments provide a more distinct separation between the modulating absorbing front protective layer 120 and the LAL 110, as well as additional design features that can be optimized.

[0037] 3D shows that in some MALALs 100, the modulated absorbing front protective layer 120 can be largely or completely separate from the LAL 110 and carried by a carrier structure 140, or simply carrier 140. The carrier structure 140 can have many different designs, including those that include a rear surface with an opening as shown, or in other designs, no opening.

[0038] 3E-3F illustrate that in some implementations, the modulating absorbing front protective layer 120 can be a separately insertable intraocular element. The modulating absorbing front protective layer 120 can be inserted into the carrier 140, or in some embodiments, simply into the capsular bag anterior to the LAL 110.

[0039] The physical extent of the modulating absorbing front protective layer 120 may be characterized, relatively speaking, as a thickness that is less than 50%, 25%, 5%, or 2% of the thickness of the light accommodating lens LAL 110. In absolute terms, the thickness of the modulating absorbing front protective layer 120 may be in the range of 1-200 microns, in some cases in the range of 1-100 microns, and in some cases in the range of 10-50 microns.

[0040] Before proceeding, we return to U.S. Patent Nos. 8,604,098 and 8,933,143, both of which are entitled "On-Demand Photoinitiated Polymerization" and issued to Boydston et al. These patents propose incorporating a "masking compound" into a light-accommodating lens to reduce the risk of unintended polymerization until the time of photoconditioning, at which point photoisomerization is triggered to allow the lens to adjust. However, the solutions proposed by these patents fail to solve the problem because the masking compound is widely distributed throughout the volume of the light-accommodating lens. Because the masking compound is dispersed throughout the lens volume, the anterior region of the light-accommodating lens is prone to forming undesirable zones where it does not receive sufficient protection, and therefore is prone to uncontrolled and undesirable changes in its optical properties.

[0041] An embodiment of the MALAL100 addresses the shortcomings of this prior proposal by concentrating the protective modulating absorbing compound 300 in a front protective layer 120 formed and positioned anteriorly relative to the LAL 110, instead of dispersing the compound 300 throughout the volume of the LAL 110. This embodiment is a structural improvement that allows the MALAL100 to fully protect even the anteriormost region of the LAL110 from UV light, since it is only the anterior placement of this protective modulating absorbing compound 300 that prevents accidental zoning and uncontrolled optical changes from implantation through tuning to lock-in of the MALAL100.

[0042] 8A-8B, the description of the MALAL 100 embodiment continues by identifying and describing a specific example of the modulatable absorption compound 300. For the sake of concreteness, this description begins by detailing a specific example before presenting numerous alternative solutions. Azobenzene is one of the compounds known to change its absorption properties upon stimulation with light. Azobenzene is one of the simplest examples of a family called azo compounds, with the general form RN=N-R', where R and R' can be aryl, alkyl, or groups thereof. Azobenzene is known to have two conformations, with different bond angles between the N=N double bond and one of the two phenyl rings. The "trans" conformation has high absorption in the UV spectrum, peaking in the wavelength range of 360-370 nm, and this absorption is π-π * This is accompanied by an electronic transition of . Similar peaks exist for various functionalized azobenzenes. UV light with a wavelength near 365 nm can act as a high-low modulation stimulus 310-htl, causing azobenzene to transition from a highly absorbing isomer 300-h in the trans conformation to a less absorbing isomer 300-l in the cis conformation. As shown, the cis conformation has significantly lower absorption near 365 nm. Thus, azobenzene is one embodiment of a modulatable absorption compound 300 in the front protective layer 120 that largely blocks incident UV light in its trans conformation 300-h but can also switch to a less absorbing cis conformation 300-l to pass modulated radiation 210 to the LAL 110. For completeness, azobenzene-based compounds can also have additional conformations.

[0043] As previously described in connection with FIG. 6, when UV light is used to illuminate LAL110, the UV light initially acts predominantly as a high-low modulation stimulus 310-htl, increasing the proportion of azobenzene-modulated absorbing compound 300 that transitions from its highly absorbing trans isomer 300-h to its less absorbing cis isomer 300-l. As the UV illumination continues to modulate the absorption of azobenzene by inducing the trans-cis transition, an increasing proportion of the UV beam passes through the front protective layer 120 to reach LAL110, where it acts as conditioning illumination 210, thus altering the optical properties of LAL110. UV illumination can be applied in a spatial profile, i.e., a nomogram, resulting in planned adjustment of the optical properties of LAL110.

[0044] As shown in Figure 5B, once the UV beam as conditioning irradiation 210 is applied with the spatial profile necessary to ultimately induce tuning of the optical properties of LAL 110, diffusion of the photopolymerizable macromer 113 begins, as shown in Figures 5C-5D. However, this diffusion can take a day or longer, and therefore LAL 110 must again be protected from uncontrolled UV illumination until lock-in irradiation 220, Figure 5E, is applied. This protection can be achieved by applying a low-to-high modulation stimulus 310-lth to reverse-transition the low-absorbing isomer 310-l to the high-absorbing isomer 300-h. In the case of azobenzene, this corresponds to a reverse transition from the cis conformation to the trans conformation. This transformation can be achieved by applying a low-to-high modulation stimulus 310-lth with substantial spectral weighting near the absorption maximum of the low-absorbing cis isomer 300-l.

[0045] In Figure 8B, the low-absorbing cis isomer 300-l is shown in n-π * We show that the LAL110 molecule has an absorption peak near 450 nm, which is associated with an electronic transition of . Therefore, illumination with a strong spectral weight near 450 nm can act as a low-to-high modulation stimulus, inducing cis-to-trans conversion and re-establishing the underlying UV protection of LAL110.

[0046] (1) Applying a low-to-high modulation stimulus 310-lth using a dedicated light source is useful in some embodiments but unnecessary in others. At least the following other agents can convert the cis conformation 300-l back to the trans conformation 300-h: (2) Thermodynamic relaxation: The trans conformation has less energy than the cis conformation, and therefore thermodynamic relaxation efficiently restores azobenzene to its initial trans conformation; and (3) as detailed below, sunlight or ambient light itself can serve as an efficient reaction accelerator to drive azobenzene into a driven steady state containing a high concentration of the trans conformation.

[0047] In general, the whole picture of photoisomerization can be thought of as a dynamic balance between trans-cis and cis-trans reactions. TIFF0007725459000001.tif42138

[0048] Here, the reaction rate can be determined by spectral integration as follows: TIFF0007725459000002.tif37130

[0049] where φ t and φ c are the quantum yields of absorption defined as photoinduced transitions / absorbed photons and are therefore dimensionless. The wavelength dependence of these quantum yields in the relevant wavelength interval is minimal and therefore can be neglected. I s (λ) is [mW / (cm 2* nm)], etc. * is the spectral irradiance of the incident radiation in units of π-π (wavelength). * The trans-cis absorption associated with the transition is λ t1 -λ t2 is induced by absorbing a photon in the range of n-π * The cis-trans absorption associated with the transition is λ c1 -λ c2These two wavelength intervals, also called absorption bands, form the boundaries of the integral. t (λ) and ε c (λ) are the [liters / (mol * cm)], etc. * is the molar absorptivity value in units of (length), and c c and c t is the concentration of the modulating absorbing compound 300 in the low-absorbing cis conformation and the high-absorbing trans conformation in the usual units of [mol / liter]. The molar extinction coefficient can also be thought of as the absorption cross section. From equations (2a)-(2b), the concentration c t / c c via the inverse time constant k t / k c Related to [(1 / sec) * (reactions / cm 3 )] and reaction rate R t / R c R therm is the rate at which the cis state thermally decays to the trans state. R therm is k therm * c c can be estimated as, where k therm can be defined as the reciprocal of the 1 / e time constant of thermal relaxation. For some typical compounds, k therm -1 The duration of the period is 1-20 hours, sometimes 1-5 days, but sometimes 10-1,000 seconds. In the presence of low-to-high modulation stimuli, including even ambient light, the R therm The term is two or three orders of magnitude smaller than the integral term and is ignored in this analysis. Furthermore, the concentration of the trans conformation is c t and the concentration of the cis conformation is given by c c Naturally, c t +c c= c0, which is the total concentration of the modulable absorbing compound 300, in this case azobenzene, which does not change over time. The speed of light is simply represented by c, and Planck's constant is represented by h. The term λ / hc=1 / hν uses these constants to calculate the spectral irradiance I s (λ) is divided by its energy hν, thereby converting the spectral irradiance from a power density to a photon number density.

[0050] In a steady state of dynamic equilibrium, the trans-cis and cis-trans rates are equal, R t =R c (3) This relationship determines the ratio of cis to trans concentrations in this dynamic equilibrium as follows: TIFF0007725459000003.tif3364(4) This leads to the following relationship between the individual cis and trans concentrations: TIFF0007725459000004.tif1426(5a) TIFF0007725459000005.tif1527(5b)

[0051] These results are based on the illumination spectral irradiance I s (λ) as it enters the modulated absorbing compound 300, and is therefore an approximation for a near-surface or thin modulated absorbing front protective layer 120. For a modulated absorbing front protective layer 120 that extends in the z-direction, i.e., depth direction, the spectral irradiance attenuates with increasing z-depth as it propagates within the front protective layer 120. A more complete treatment would be to characterize the effect of this attenuation on absorption as the z-depth dependent spectral irradiance I s (λ, z) and integrate the rate of the absorption process along the z-depth. The results of such in-depth analyses are often well approximated by the above equation. Below, we further analyze the effect of the depth dependence of irradiance.

[0052] First, consider the case of a high-low modulation stimulus 310-htl. In a typical case, such a stimulus 310-htl can be applied by a powerful UV light source, such as a mercury lamp or a UV LED. Such light sources often produce illumination with a fairly narrow bandwidth. This can be approximated by a Dirac delta centered at 365 nm, the standard wavelength of a mercury lamp, which simplifies the integral to a product, resulting in a simple expression for the concentration ratio a of such a light delivery device LDD. TIFF0007725459000006.tif1850(6)

[0053] In azobenzene, φ t ≒0.15 and φ c ≒0.5, and the ratio of molar absorbances is about 0.1, so a LDD This means that when a UV light source is used as the light source for the high-low modulation stimulus 310-htl, the concentration of the trans conformation c t is the concentration of cis conformation c c A dynamic equilibrium is induced in which the trans conformation is approximately one-third of the original concentration, thus leaving only about 25% of the modulating absorbing compound 300 in the trans conformation compared to an initial concentration of about 100%. This approximately four-fold reduction in the trans conformation concentration is sufficient, for a suitably selected thickness of the front protective layer 120, to allow a large portion of the subsequent conditioning irradiation 210 to pass through the front protective layer 120 and into the LAL 110. One aspect of the above derivation worth clarifying is that application of the high-low modulation stimulus 310-htl does not result in a complete switch of all of the high absorbing isomer 300-h to the low absorbing isomer 300-l, but rather results in a partial modulation and transition.

[0054] Next, we describe the reverse process, low-high modulation stimulus 310-lth, in the particularly simple case where no explicit light source is applied, but rather the concentrations of the two conformations are simply controlled by the ambient light. In this case, the spectral irradiance I swhere (λ) is that of solar radiation in the case of direct exposure, i.e., when the patient is looking directly at the sun. Equation (4), which affects the concentration ratio, is controlled only by the solar irradiance ratio, and the diffuse effect cancels out from this ratio, so the concentration ratio a does not change with indirect diffuse exposure, where only diffuse sunlight reaches the eye.

[0055] Because the cornea efficiently absorbs short-wavelength UV light, the magnitude of solar irradiance below 300 nm reaching the IOL can be neglected, as can the molar absorption above 500 nm of the azobenzene and related compounds under consideration. Thus, integrating equation (4) over the wavelength range λ = 300 nm to 500 nm, which encompasses solar spectral irradiance, yields: TIFF0007725459000007.tif3677(7)

[0056] For some azo compounds, such as those described below, equation (7) gives a concentration ratio of about 3. For some other modulable absorption compounds 300, a is in the range of 5 to 10. These values are similar to c for a = 3. t =75%, a=5~10, c t = 84-91% trans conformation concentration. A front protective layer 120 with a modulatable absorbing compound in its high absorbing conformation 300-h at a concentration in the range of 75-91% can provide robust UV protection to the underlying LAL 110.

[0057] For completeness, several different embodiments of the low-to-high modulation stimulus 310-lth can be employed in various MALALs 100. (1) As described herein, simple exposure of the patient to ambient light can increase the concentration of the highly absorbing isomer 300-h to a level that allows it to function as an efficient anterior protective layer 120. For an anterior protective layer thickness of 10-100 μm, or in some cases 20-50 μm, and an overall molar concentration of c0 in the range of 10-100 millimolar, or in some cases 20-30 millimolar, the time for this concentration increase can be in the range of 1-10 seconds. Such switching times can be accommodated naturally in an ophthalmologist's office after the adjustment step of FIG. 5B or the lock-in step of FIG. 5E without the risk of forming uncontrolled zones in the LAL 110 during this very short time. (2) In other embodiments, a dedicated light source can be used as the source of the low-to-high modulation stimulus 310-lth to induce an even faster switching transition back to the highly absorbing isomer 300-h. For example, a solar simulator, white light flashlight, or more powerful illumination source could be employed, potentially with a UV filter to maximize the rate of conversion from 300-l to 300-h. (3) Finally, because the energy of the high-absorbing isomer 300-h is lower than that of the low-absorbing isomer 300-l, the modifiable absorbing compound also reverts to the protective high-absorbing conformation 300-h by simple thermal relaxation. As noted above, this process can be approximately 100 times slower with azobenzene, but without the use of a distinct low-to-high modulation stimulus 310-lth, this still takes only a few minutes. Thus, simply leaving the patient in simple office lighting conditions for a few minutes after treatment can restore the protective effect of the front protective layer 120.

[0058] The above discussion shows that modulatable absorbing compounds 300 having a concentration ratio a<<1 for narrowband UV modulating stimuli 310-htl while having a concentration ratio a>>1 for solar radiation or distinct low-high modulating stimuli 310-lth are suitable for providing two beneficial effects: (1) such modulatable absorbing compounds 300 can protect MALAL100 from uncontrolled optical adjustments caused by unconscious patient non-compliance from implantation to lock-in, and (2) at the same time, they can enable the application of modulated illumination 210 due to conformational changes caused by the modulating stimuli 310.

[0059] We now return to the issue of the attenuation of spectral irradiance with increasing z-depth. It is worth noting that this attenuation only enhances the usefulness of MALAL 100, as it induces a "self-shading effect." In a preferred embodiment of ambient solar radiation acting as the low-high modulation stimulus 310-l, the solar radiation I decreases as it propagates deeper into the front protective layer 120. s The UV part of (λ, z) is absorbed faster than the visible part. This is because the t This is because in the presence of a realistic amount of trans-high absorbing isomer 300-h, such as >25%, the extinction coefficient in the UV region is higher than the extinction coefficient in the visible region. Specifically, for a typical modulated absorbing compound 300 containing both trans-high absorbing isomer 300-h and cis-low absorbing isomer 300-l, this corresponds to ε(λ=365 nm)>ε(λ=450 nm). Applying Equation (7) to the concentration ratio a solar In the UV region, the spectral irradiance I s When (λ,z) decays faster, a solar It can be seen that the deeper one goes into the front protective layer 120, the fewer UV photons will cause the modulated absorbing compound 300 to transition from the trans high absorbing isomer 300-h to the cis low absorbing isomer 300-l, while relatively more visible photons will drive the reverse process from the cis low absorbing isomer 300-l to the trans high absorbing isomer 300-h, thereby increasing the a with increasing depth. solarThis increases the overall protective UV blocking function of the front protective layer 120.

[0060] Next, we clarify another aspect of the depth dependence of spectral irradiance. The overall reduction in spectral irradiance exiting the front protective layer 120 through the distal surface is controlled by absorbance, which is given by the product of the molar extinction coefficient ε of the modifiable absorbing compound 300, the molar concentration c of the modifiable absorbing compound 300, and the thickness D of the front protective layer 120. In optical design terminology, absorbance is sometimes referred to as optical density. Thus, different embodiments of the front protective layer 120 including different modulatable absorbing compounds 300 with different molar extinction coefficients at different molar concentrations and with different thicknesses will provide approximately the same protection as long as the product of these three quantities is the same. The ultimate selection of the modulatable absorbing compound 300, its concentration, and its thickness can be driven by further considerations, such as a desire to avoid excessive yellowing of the patient's visual experience.

[0061] Before proceeding, it is useful to summarize the potential advantages of the MALAL 100 with the front protective layer 120 described above over existing designs, some of which have already been mentioned above.

[0062] (1) The MALAL 100 with the front protective layer 120 can significantly reduce the risk of uncontrolled optical changes in the LAL 110 due to accidental non-compliance by the patient, such as forgetting to wear UV-blocking glasses.

[0063] (2) Furthermore, MALAL 100 can employ a significantly lower concentration of UV absorber 116 dispersed throughout the volume of LAL 110. Such LAL 110 requires a significantly lower dose for lock-in irradiation 220. Any reduction in the dose of UV lock-in irradiation of MALAL technology further enhances the safety of the procedure.

[0064] (3) A MALAL 100 with a more absorbent front protective layer 120 can even provide such effective UV blocking that the patient does not need to wear UV blocking glasses from implantation through adjustment and lock-in. This is highly beneficial because such a MALAL 100 essentially eliminates the risk posed by accidental patient non-compliance and greatly improves patient comfort from implantation to lock-in.

[0065] (4) A MALAL 100 with a more highly absorbing front protective layer 120 may even eliminate the lock-in step of FIG. 5E. The UV blocking by the front protective layer 120, once restored to its highly absorbing isomer 300-h after conditioning irradiation 210, can be so efficient and robust that it can completely prevent UV radiation from entering the LAL 110 for very long periods of time, such as years and decades. In such highly protected MALAL 100, even if the LAL 110 contains significant concentrations of unpolymerized photopolymerizable monomers and macromers 113 left over from the conditioning step of FIG. 5B, the robust, long-term UV absorption by the front protective layer 120 ensures that the unpolymerized monomers and macromers 113 will not be photopolymerized by solar irradiation for years and decades, thereby ensuring that the MALAL 100 maintains and provides the optical performance established by conditioning irradiation 210 during the conditioning step of FIG. 5B. Such a "no lock-in" MALAL can reduce the number of visits required for the patient to a single adjustment procedure.

[0066] (5) It is also worth noting that in some patients, the implanted MALAL100 may not shift or tilt. These patients may report that their vision remains of high quality with no significant deterioration after implantation. For these patients, physicians may conclude that no follow-up visits for MALAL100 adjustments are necessary. For all patients who may need to travel long distances, possibly even by plane, for adjustments and / or lock-in procedures, the potential elimination of any kind of follow-up visit can mean a further qualitative improvement in the overall experience or "journey" for these patients.

[0067] (6) Finally, in a small percentage of cases, unexpected changes may occur in the eye after cataract surgery due to various other ophthalmic deteriorations, injuries, or shocks of any kind. In such cases, the fact that such a lock-in-free MALAL100 remains adjustable can be extremely beneficial, as it can adjust to accommodate unexpected developments even years after implantation.

[0068] There are many other embodiments of the modulating absorption compound 300 besides azobenzene. The modulating absorption compound 300 can be an azoaromatic compound, a diazene, an azopyrazole, a dienylethene, a fulgide, an azulene, a spiropyran, an ethene aromatic compound, a macromer of one of these compounds, a polymer of these compounds, a composition including one of these compounds, a composition including one of these compounds as a side chain, a composition including one of these compounds as a main chain with side chains, nanoparticles attached to one of these compounds, and one of these compounds dissolved in an ionic fluid. The modulating absorption compound 300 can also be a polymer in which any of the above compounds is incorporated into the polymer host matrix 112 itself, and therefore need not be incorporated as a side chain. Some such compounds can also include polymers that flex in response to light. The discussion continues by reviewing an extensive list of modulating absorption compound 300 embodiments.

[0069] As mentioned above, the azo aromatic compound can be, for example, an azobenzene, which exhibits the following conformational change [1]: TIFF0007725459000008.tif67101[1]

[0070] In another embodiment of the modulated absorption compound 300, the azo aromatic compound can be 4-methoxyazobenzene [2]. TIFF0007725459000009.tif2883[2]

[0071] The modulated absorption compound 300 can also be an indazole as shown in [3]-[6], an allylated azobenzene with various spacer links, or another version of a phenylazopyrazole. TIFF0007725459000010.tif48142[3] TIFF0007725459000011.tif50143[4] TIFF0007725459000012.tif5266[5] TIFF0007725459000013.tif45153[6]

[0072] FIG. 9 shows that in yet another embodiment, the azopyrazole can be vinylphenylazopyrazole (“VPAP”) [7] with the extinction coefficient shown. TIFF0007725459000014.tif39126[7]

[0073] Finally, in some embodiments, the ethene-aromatic compound can be a stilbene [8]. TIFF0007725459000015.tif3966[8]

[0074] 10A-10B illustrate further aspects of an embodiment of modulatable absorption compound 300. These figures show the dependence of the extinction coefficient curves on the power density of the high-low modulated stimulus 310-htl for 4-aminoazobenzene in FIG. 10A and for 4-(4'hydroxyphenylazobenzoic acid) in FIG. 10B. As can be seen, 4-aminoazobenzene exhibits a 10 mW / cm 2 applied for 60 seconds. 2 whereas 4-(4'hydroxyphenylazobenzoic acid) has already transitioned from its high absorbing isomer 300-h to its low absorbing isomer 300-l in response to a low power density or irradiance of 100 mW / cm applied over the same 60 seconds by a high-low modulation stimulus 310-htl. 2 The choice of the particular modulatable absorption compound 300 used in a particular embodiment of the MALAL 100 is dependent on the characteristics shown in Figures 10A-10B, as well as the quantum yield φ seen in equations (1)-(7) above. t and φ c For example, some MALAL100s have a radiation intensity of about 3 mW / cm (integrated over the 250-500 nm portion of the solar spectrum). 2 The solar power density of 300-h can be designed so that only power densities much higher than the irradiance should induce the conversion of the high absorbing isomer 300-h to the low absorbing isomer 300-l. In some cases, these power densities or irradiances can be determined by integrating the spectrum over a narrower wavelength range, such as 300-450 nm.

[0075] Figures 11 and 12A-12B illustrate another characteristic of MALAL 100: the time evolution of the extinction coefficient as the high-absorbing trans isomer 300-h transitions or changes to the low-absorbing cis isomer 300-l when vinylphenylazopyrazole (VPAP) is the modulated absorbing compound 300. In Figure 11, the absorption curves are captured with the duration of the high-low modulation stimulus 310-htl swept from 0 to 60 seconds. Similar to the above, different MALAL design principles may favor modulated absorbing compounds 300 with one type of time dependence over another.

[0076] In Figure 12A, the time dependence of the extinction coefficient near 450 nm is zoomed in to show the extinction coefficient curve when a high-low modulation stimulus 310-htl is applied over a duration of 0 to 30 seconds. (Note that the quantity shown in Figure 12 is the absorbance that characterizes the absorption throughout MALAL 110. This absorbance tracks the molar extinction coefficient shown in Figures 9-10, which is typically measured in solution. This absorbance also has a contribution from UV absorbers 116 dispersed in MALAL 110, which further provides significant absorbance below wavelengths of approximately 400 nm.) UV radiation exposure was 150 mJ / cm. 2 FIG. 12B plots the time dependence of the extinction coefficient or related absorbance at a specific wavelength of 448 nm as a function of the duration of the modulation stimulus 310. These curves show that the high-low modulation stimulus 310-htl was fixed at 150 mJ / cm. 2 We demonstrate that when exposed to UV radiation of 1000 nm, the modulated absorption compound VPAP300 can be largely converted to its low extinction coefficient isomer 300-1 over a period of approximately 20 seconds, which is short enough to demonstrate that this absorption-modulated MALAL technology meets the promise of efficient photoprocessing.

[0077] In many other embodiments of the MALAL 100, the high-low modulation stimulus 310-htl can include high-low illumination with light having a band centered on a wavelength in the range of 300-400 nm, and the low-high modulation stimulus 310-lth can include low-high illumination with light having a band centered on a wavelength in the range of 300-700 nm, which includes the solar spectrum. In other words, when referring to illumination and its wavelength, this wavelength refers to illumination having a band with a central peak at the referenced wavelength, and the band also has a bandwidth around this central wavelength, because the source of the illumination is often not a coherent laser and therefore has a finite bandwidth, i.e., spectral spread. In the high-low modulation stimulus 310-htl, the source can be a narrowband source, such as a mercury lamp or UV LED, whose band width can range from 1 to 50 nm, and in other embodiments, can range from 1 to 10 nm. With low-to-high modulation stimulation 310-1th, this source can have an extremely wide bandwidth that even encompasses the normal solar spectrum, which ranges from about 300 nm to over 2,500 nm.

[0078] As noted above, in some modulatable absorption compounds 300, naturally occurring thermal relaxation may already be sufficient to fulfill the role of low-to-high modulation stimulus 310-lth by inducing a transition from low-to-high absorbing chromophore 300-l to high-to-high absorbing chromophore 300-h. For MALAL100, which thermally relaxes low-to-high absorbing chromophore 300-l to high-to-high absorbing chromophore 300-h, describing the light source as having a band-centered peak and bandwidth is not a natural characterization.

[0079] In some embodiments of MALAL100, the terms "low absorption" and "high absorption" can be quantitatively specified. In some MALAL100, the ratio of the extinction coefficient of the high absorption conformation 300-h to the extinction coefficient of the low absorption conformation 300-l at wavelengths in the 300-400 nm range can be greater than 2. As an example, as shown in FIG. 10A, the 4-aminoazobenzene-based modulated absorption compound 300 has an extinction coefficient ratio of approximately 5 when a reference wavelength of 350 nm is selected. This extinction coefficient ratio can also be referred to as the contrast ratio. For some purposes, other wavelength values, such as wavelengths in the 360-370 nm range, can also be selected. In some of these embodiments, the extinction coefficient ratio can be greater than 3, and in some cases, even greater than 4.

[0080] In many embodiments of MALAL100, the high absorbing conformation 300-h of the modulated absorbing compound 300 has a lower energy than the low absorbing conformation 300-l. Thus, at equilibrium and ambient conditions, the ratio of the concentration of the high absorbing isomer 300-h to the concentration of the low absorbing isomer 300-l is greater than 2 in at least one of the solid phase, dilute solution, and host matrix bound state. In low light conditions, the energies of these high absorbing isomer 300-h and low absorbing isomer 300-l control the density ratio of these isomers at ambient conditions according to the exponential activation factor of statistical mechanics.

[0081] In some MALALs, the modulated absorption compound 300 provides an absorbance of 1 mJ / cm integrated over the wavelength range of 300 nm to 400 nm. 2 ~1,000mJ / cm 2 The compound may have a chemical composition such that under high to low irradiation 310-htl in a range of radiation exposure, at least 25% or 50% of the high absorbing conformation 300-h transitions to the low absorbing conformation 300-l.

[0082] Here, the lighting irradiance is mW / cm 2 Radiant exposure is measured in mJ / cm 2 It is recalled that radiant exposure is measured in units of irradiance. Roughly speaking, radiant exposure = irradiance* irradiance as time. However, in some embodiments of MALAL 100, this relationship may be more complicated than a simple product. The amount of absorption modulation of MALAL 100 for a modulated stimulus 310 with twice the irradiance but half the time may be different, even though the product of these two factors is the same. Such a nonlinear relationship is sometimes called a violation of reciprocity. This violation can occur, for example, when the thermal relaxation rate R in Equation (2b) thermal occurs when the rate of thermal relaxation is fast and comparable to other rates of thermal relaxation.

[0083] Similar characterizations can be applied to the inverse conversion. In some MALAL 100 embodiments, the modulatable absorption compound 300 provides an absorption of 1 mJ / cm over the wavelength range of 300 nm to 700 nm. 2 ~1,000mJ / cm 2 The low-high modulation stimulus 310-l may have a chemical composition such that at least 50% of the low-absorbing conformation 300-l transitions to the high-absorbing conformation 300-h under a low-high modulation stimulus 310-lth with a radiation exposure in the range of 100 nm to 150 nm. In many embodiments, the source of the high-low modulation stimulus 310-htl and the source of the conditioned illumination 210 may be selected to be the same shared source, such as a UV source. A typical example may be a mercury arc lamp or a UV LED with a spectral peak near 365 nm. In contrast, in most embodiments, the source of the low-high modulation stimulus 310-lth typically operates at a longer wavelength with a much broader spectrum, and thus differs from the shared source. As mentioned above, for the related class of MALAL100, the ambient light in a doctor's office itself, which emits radiation in a spectrum that can be mostly concentrated in the visible range of 400 to 700 nm, may be an effective source of the low-high modulation stimulus 310-lth.

[0084] Another way to characterize the effect of the modulation stimulus 310 is to measure the quantum yields φ of the trans-cis and cis-trans transitions. t and φ c In such a case, the modulably absorbing compound 300 has a quantum yield φ of the transition from the high absorbing conformation 310-h to the low absorbing conformation 310-l.t Some MALAL100s have a chemical composition such that the quantum yield φ is greater than 1%. t can be higher than 5%, and for some MALAL100s, higher than 10%. The higher the quantum yield, the less radiation exposure is required to cause the high absorbing conformation 310-h to transition to the low absorbing conformation 310-l. Here, quantum yield is defined in the conventional form: quantum yield = number of induced transformations / number of absorbed photons.

[0085] Using the concept of quantum yield, modulatable absorbing compound 300 can be further characterized as follows: modulatable absorbing compound 300 has a quantum yield φ for transitioning from high absorbing isomer 300-h to low absorbing isomer 300-l in response to high-low modulation stimulus 310-htl. t is in the range of 1-20%, and the quantum yield φ of the reverse transition from the low-absorbing isomer 300-l to the high-absorbing isomer 300-h in response to a low-to-high modulation stimulus 310-lth c In other embodiments, the quantum yields of these two elements may be in the range of 10 to 70%. t =5~10% and φ c = 40-60%.

[0086] FIG. 13 shows that several days after the conditioning procedure concluded in FIG. 5D, the increased refractive power of MALAL 100 needs to be locked in by lock-in irradiation 220 as shown in FIG. 5E. However, the unpolymerized photopolymerizable macromer 113 needs to be protected from accidental UV irradiation during the time between the end of the conditioning procedure and the lock-in procedure. To achieve this protection, the modulatable absorbing compound 300 of the front protective layer 120 can switch back to the high-absorbing conformer 300-h at the end of conditioning irradiation 210 in FIG. 5B, and only transition from the high-absorbing conformer 300-h to the low-absorbing conformer 300-l again at the start of lock-in irradiation 220 in FIG. 5E. Clearly, the modulatable absorbing compound 300 needs to be repeatedly transitionable or switchable when absorbing high-low modulation stimuli 310-htl and low-high modulation stimuli 310-lth. FIG. 13 shows the absorbance of modulatable absorption compound 300 after repeated back-and-forth modulation, where modulatable absorption compound 300 is a vinylphenylazopyrazole. This figure zooms in on the cis-trans absorption peak near 450 nm. FIG. 13 also shows that the absorption spectrum remains essentially unchanged after six back-and-forth switchings, making at least some embodiments of modulatable absorption compound 300 suitable for repeated modulation between high and low absorption conformations. Some modulatable absorption compounds 300 have been demonstrated to be capable of repeated switching between 1,000 and 1,000,000 times with minimal or even imperceptible degradation.

[0087] In some embodiments, the modulated absorption compound 300 comprises a photoisomerizable moiety linked to one or more polymerizable moieties. In some embodiments, the modulated absorption compound 300 is represented by the following formula [9]: TIFF0007725459000016.tif1241[9] wherein Y is a photoisomerizable moiety (e.g., as described above), n1 and n2 are each independently 0, 1, 2, or 3, and each Z 1 and Z 2 is independently a polymerizable moiety or a cross-linking moiety linked to Y via an optional linker.

[0088] In some embodiments, in formula [9], n1 and n2 are each 1, and Z 1 and Z 2 are each independently linked to Y via a linker 1 to 20 atoms in length (e.g., 1 to 6 atoms in length). In some embodiments, n1 is 2 or 3, and each Z 1 is attached to Y via a branched linker (e.g., an amino- or ammonium-containing linker). In some embodiments, when n1 and / or n2 are 2 or 3, each Z 1 and / or Z 2 are independently linked to Y via an unbranched linear linker. In some embodiments, Y is an azoarylene, diarylethene, or dithienylethene. In some embodiments, each Z 1 and Z 2 are independently selected from vinyl, vinylidene, diene, olefin, allyl, acrylate, acrylamide, and acrylic acid.

[0089] In some embodiments, in formula [9], the modulable absorbing compound 300 has the structure Ar 1 -N=N-Ar 2 or Ar 1 -C=C-Ar 2 where Ar 1 and Ar 2 are independently selected from aromatic six-membered rings that may be substituted or unsubstituted and may contain one or more heteroatoms. In some embodiments, the modulatable absorption compound 300 is selected from the group consisting of (e.g., Ar 1 and Ar 2 In some embodiments, the modulable absorption compound 300 comprises an azobenzene moiety, such as Ar 1 -N=N-Ar 2 As illustrated for the compound, the trans isomer can be photoisomerized to the cis isomer. In some embodiments, the cis isomer of modulative absorbing compound 300 spontaneously reverses to the trans isomer. TIFF0007725459000017.tif33128

[0090] In some embodiments, the azobenzene moiety is a photoisomerisable chromophore that has an absorption maximum near a photoinitiator (such as any of the photoinitiators used and described herein), hi some embodiments, the azobenzene moiety has an absorption maximum that is about 50 nm or less (e.g., about 40 nm or less, about 30 nm or less, about 20 nm or less, or about 10 nm or less) from the absorption maximum of the photoinitiator.

[0091] In some embodiments, the thermodynamically more stable trans-azobenzene (t-AB) moiety tends to absorb at lower wavelengths than the corresponding cis-azobenzene (c-AB) isomer. Upon irradiation, photoisomerization can be facile and quantitative. In some embodiments, thermal relaxation of the c-AB moiety to the t-AB isomer occurs within a few hours (e.g., within 12 hours, such as within 6 hours, 5 hours, 4 hours, 3 hours, 2 hours, or 1 hour) at ambient temperature. Irradiation of the t-AB moiety near its absorption maximum results in isomerization to the cis isomer, resulting in a change in the absorption spectrum (e.g., a shift in the absorption maximum).

[0092] In some embodiments, the modulated absorption compound 300 further comprises a polymerizable moiety, i.e., a functional group that is polymerizable in the prepolymer composition upon application of a suitable stimulus (e.g., activation of a photoinitiator). The polymerizable moiety can include functional groups such as alkenyl, vinyl, vinylidene, diene, olefin, allyl, acrylate, or (meth)acrylic functional groups. In some embodiments, the polymerizable moiety is an allyl or vinyl group.

[0093] In some embodiments, when the modulating absorption compound 300 includes a polymerizable moiety, the modulating absorption compound 300 can be chemically incorporated into another component of the composition of interest. For example, the modulating absorption compound 300 can be incorporated into the backbone of a polymer present as a matrix material (see below). Also, for example, the modulating absorption compound 300 can be incorporated into the backbone or as a side group of a prepolymer (see below). In this manner, small molecule modulating absorption compounds 300s can be chemically incorporated into a polymer component of the composition of interest. In some embodiments and applications, incorporating the modulating absorption compound 300s in this manner reduces the likelihood of masking components diffusing out of the composition of interest.

[0094] In some embodiments, the modulable absorbing compound 300 is represented by the structure of formula

[10] : TIFF0007725459000018.tif41116

[10] where: n 3 and n 4 are each independently 0, 1, 2, or 3; (Z 3 ) n3 -L 3 - and -L 4 -(Z 4 ) n4 can be independently absent or present, each Z 3 and Z 4 is independently a polymerizable or crosslinkable moiety; L 3 and L 4 is the linker, n 5 and n 6 are each independently 0, 1, 2, 3, 4 or 5, 3 ) n3 -L 3 -n if present 5 is not 5, but -L 4 -(Z 4 ) n4If there exists n 6 is not 5, Each R is independently selected from the group consisting of hydrogen, hydrocarbyl (e.g., alkyl, alkenyl, allyl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, and sulfonamide.

[0095] In some embodiments, in formula

[10] , each Z 3 and Z 4 are independently selected from vinyl, vinylidene, diene, olefin, allyl, acrylate, acrylamide, and acrylic acid.

[0096] In some embodiments, in formula

[10] , L 3 and L 4 are each independently a linker 1 to 20 atoms in length, such as a linker 1 to 6 atoms in length. In some embodiments, the linker L 3 and / or L 4 When present, these may contain amino groups linking the polymerizable or cross-linkable moieties. In some embodiments, linkers containing branched amino groups (e.g., trivalent amino groups or tetravalent ammonium groups) are present to link two or three polymerizable and / or cross-linkable moieties to the azobenzene. In some embodiments, L 3 and / or L 4 is a branched amino (-N=) group. In some embodiments, L 3 and / or L 4 is a branched ammonium (-N(+)=) group. In some embodiments, L 3 contains a branched amino group or an ammonium group, and n 3 is 2 or 3, and Z 3 is allyl or vinyl.

[0097] In some embodiments, in formula

[10] , L 3 and L 4When present, they can be attached to the azobenzene ring at any convenient position. For example, L 3 can be attached to the first phenyl ring at the 2, 3, or 4 position relative to the azo substituent. For example, L 4 L can be attached to the second phenyl ring at the 2', 3', or 4' position relative to the azo substituent. 3 and / or L 4 All combinations of L are contemplated, each arranged around the first and second phenyl rings. For example, L 3 and L 4 can be attached at the 2 and 2' positions, respectively. For example, L 3 and L 4 can be attached at the 3 and 3' positions, respectively. For example, L 3 and L 4 can be attached at the 4 and 4' positions (i.e., para), respectively. 3 can be attached to the 4-position of the first phenyl ring, and L 4 can be attached to the 2' position of the second phenyl ring. 3 and L 4 1 shows an exemplary arrangement of

[0098] In some embodiments, the modulable absorbing compound 300 is represented by the structure of formula

[11] : TIFF0007725459000019.tif3992

[11] where L 3 and L 4 is the linker, n 5 and n 6 are each independently 0, 1, 2, 3, or 4; Each R is independently selected from the group consisting of hydrogen, hydrocarbyl (e.g., alkyl, alkenyl, allyl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, and sulfonamide.

[0099] In some embodiments, the modulated absorption compound 300 is as represented by

[11] , except that one or both of the terminal allyl groups can be independently substituted with any convenient polymerizable or crosslinkable moiety as described herein.

[0100] In some embodiments, in formula

[11] , L 3 and L 4 One or both of L are linked to the azobenzene via an electron withdrawing substituent such as a carbonyl, ester, amide, sulfonyl, or sulfonamide. 3 and L 4 Independently -(CH2) m1 -Z 4 -(CH2) m2 - and m 1 and m 2 are each independently 0 or an integer of 1 to 6, and Z 4 is selected from a carbonyl (-C(=O)-), an ester (-C(=O)O-), an amide (e.g., -C(=O)NH-), a carbamate (e.g., -OC(=O)NH-), a sulfonyl (-SO-), a sulfonamide (e.g., -SONH-), an ether (-O-), a thioether (-S-), or a urea group (e.g., -NHC(=NH)NH-). In some embodiments, m 1 is 2 and m 2 is 0. In some embodiments, Z 4 is -O-.

[0101] In some embodiments, the modulable absorption compound 300 is represented by one of the following formulas

[12] -

[14] : TIFF0007725459000020.tif3697

[12] TIFF0007725459000021.tif45107

[13] TIFF0007725459000022.tif4995

[14] where L 3 , L4 , (R) n5 and (R) n6 is as defined above for formula

[11] . In some embodiments, L 3 and L 4 are independently -O- and -O(CH2) m -, where m is an integer from 1 to 6 (e.g., m is 2). In certain embodiments, each R is hydrogen.

[0102] In some embodiments, the modulable absorbing compound 300 is represented by the structure of formula

[15] or

[16] : TIFF0007725459000023.tif5382

[15] TIFF0007725459000024.tif5680

[16] where R 1 ~R 8 are each independently selected from the group consisting of hydrogen, hydrocarbyl (e.g., alkyl, alkenyl, allyl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, and sulfonamide.

[0103] In some embodiments, in formula

[15] or

[16] , R 1 ~R 8 One or more of the following is -L 5 -O-CH2CH=CH2, where L 5 is an optional linker group. In some embodiments, in formula

[15] or

[16] , each L 5 is a C1-C6 alkyl chain (e.g., C2 alkyl). In some embodiments, in formula

[15] or

[16] , each L 5 In some embodiments, in formula

[15] or

[16] , R 1 ~R 8 are hydrogen atoms.

[0104] In some embodiments, the modulable absorbing compound 300 is represented by the structure of formula

[17] : TIFF0007725459000025.tif4390

[17] where A is a heterocycle, n 7 is 0 or an integer from 1 to 5, Each R is hydrogen, 1, 2, or 3, where m is -L 5 -(Z 5 ) m , hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, and sulfonamide; R 11 ~R 15 is hydrogen, hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, sulfonamido; hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl, and sulfonamido; 5 -Z 5 are each independently selected from the group consisting of: L 5 is a linker, and each Z 5 are independently polymerizable or crosslinkable groups.

[0105] In some embodiments, in formula

[17] , A is an N-linked heterocycle such as, but not limited to, morpholino, thiomorpholinopiperidino, piperazino, homopiperazine, azepano, or pyrrolidino. In some embodiments, in formula

[17] , A is an N-linked heterocycle (e.g., N-morpholino or N-piperidinyl).

[0106] In some embodiments, the modulable absorbing compound 300 is represented by the structure of formula

[18] : TIFF0007725459000026.tif5181

[18] where Y is O or NR 21 and R 21 is hydrogen, alkyl, aryl, acyl, heterocycle or -L 3 -Z 3 and R 16 ~R 20 is hydrogen, hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), heterocycle, halogen, haloalkyl or perhaloalkyl (e.g., trifluoromethyl), amino, hydroxyl, ether, nitro, cyano, carboxy, acyl, amide, ester, thiol, thioether, sulfonyl and sulfonamide, and -L 5 -Z 5 are each independently selected from the group consisting of: L 5 is a linker and Z 5 is a polymerizable group or a crosslinkable group.

[0107] In some embodiments, in formula

[18] , each L 5 are independently C1 to C6 alkyl chains (eg, C2 alkyl).

[0108] In some embodiments, in formula

[18] , R 16 ~R 20 and R 21 In some embodiments, in formula

[18] , at least one (e.g., two) of R16 ~R 20 and R 21 In some embodiments, in formula

[18] , at least one of R 18 Ga-(CH2) m1 -L 6 -(CH2) m2 -Z 6 and m 1 and m 2 are each independently 0 or an integer of 1 to 6, and L 6 is selected from a carbonyl (-C(=O)-), an ester (-C(=O)O-), an amide (e.g., -C(=O)NH-), a carbamate (e.g., -OC(=O)NH-), a sulfonyl (-SO-), a sulfonamide (e.g., -SONH-), an ether (-O-), a thioether (-S-), or a urea group (e.g., -NHC(=NH)NH-). In some embodiments, m 1 is 2 and m 2 is 0. In some embodiments, L 6 is -O-.

[0109] In some embodiments, R 16 ~R 20 and R 21 At least one of (e.g., R 18 , R 19 or R 20 ) is -L 7 -O-CH2CH=CH2, and L 7 is an optional linker group, optionally a C1-C6 alkyl chain (eg, a C2 alkyl).

[0110] In some embodiments, in formula

[18] , Y is O. In some embodiments, in formula

[18] , R 16 ~R 20 In some embodiments, in formula

[18] , one or more of R 18 is nitro and R 16 , R 17 , R 19 and R 20 is hydrogen.

[0111] In some embodiments, the modulative absorption compound 300 is selected from one of the following formulas

[19] -

[25] : TIFF0007725459000027.tif3961

[19] TIFF0007725459000028.tif4343

[20] TIFF0007725459000029.tif4390

[21] TIFF0007725459000030.tif4674

[22] TIFF0007725459000031.tif4581

[23] TIFF0007725459000032.tif35110

[24] TIFF0007725459000033.tif3673

[25]

[0112] To avoid undesired photoinitiated polymerization or crosslinking induced by ambient sunlight during healing, a modulating absorption compound 300 is included in the front protective layer 120 to block such photoinitiation by absorbing the UV component of the incident light. The photoinitiator 115 and the modulating absorption compound 300 can be selected to have overlapping absorption spectra to absorb enough ambient UV to prevent activation of the photoinitiator 115. Upon application of a high-low modulation stimulus 310-htl, photoisomerization of the high extinction coefficient isomer 300-h of the modulating absorption compound shifts the absorption maximum of the modulating absorption compound 300 away from the absorption maximum of the photoinitiator 115, thereby significantly reducing the overlap of the absorption spectra of the photoisomerized modulating absorption compound 300 and the photoinitiator 115 at wavelengths suitable for activation of the photoinitiator 115.

[0113] In some embodiments, photoisomerization of modulative absorption compound 300 occurs via cis-trans isomerization, a cyclization reaction, or a ring-opening reaction. Useful photoisomerizable compounds include those that can block absorption by photoinitiator 115 and exhibit a significant shift in absorption maximum upon application of a suitable modifying stimulus 310. In some embodiments, modulative absorption compound 300 undergoes cyclization or ring-opening photoisomerization upon absorption of modifying stimulus 310.

[0114] In some embodiments, the modulated absorption compound 300 comprises a photoisomerizable moiety that is a stilbene (e.g., azastilbene), an azobenzene moiety, an azoarylene, a fulgide, a spiropyran, a naphthopyran, a quinone, a spirooxazine, a nitrone, a triarylmethane (e.g., triphenylmethane), a thioindigo, a diarylethene, a dithienylethene, or an overcrowded alkene. In some embodiments, the modulated absorption compound 300 comprises an alkenyl (C=C) or azo moiety (-N=N-) moiety that undergoes photoisomerization via a cis-trans transition. In some embodiments, the modulated absorption compound 300 comprises a diarylethene that undergoes photoisomerization via an electrocyclic cyclization reaction. In some embodiments, the modulated absorption compound 300 comprises a spiropyran that undergoes photoisomerization via a ring-opening transition.

[0115] In some embodiments, the photoisomerizable moiety is selected from azoarylene, diarylethene, and dithienylethene.

[0116] In some embodiments, photoisomerization of modulably absorbing compound 300 produces a thermally unstable second isomer, e.g., the second isomer reverts to the first isomer upon removal of the light source. In such cases, photoisomerization is reversible.

[0117] In some MALALs 100, the modulated absorbing front protective layer 120 provides an absorbing power of 3 mW / cm 2A maximum of 10,000 mJ / cm2 integrated over the wavelength range of 300 nm to 400 nm at an exposure not exceeding 2 In some embodiments, the radiation exposure can be up to 50,000 mJ / cm 2 or more. 2 It can be said that:

[0118] 14A-14C illustrate another, more attractive aspect of the embodiment of the MALAL 100 described herein. Due to the presence of the modulated-absorbing front protective layer 120, even in the extremely rare event of exposure to an excessive amount of UV radiation, only a small fraction of the incident UV radiation can pass through the front protective layer 120. Thus, even if a zone 20 is formed in such an unlikely event, its size is significantly smaller than the zone formed in an LAL without such a front protective layer 120, as shown in, for example, FIGS. 2A-B. FIG. 14A illustrates the formation of a very small zone 20 in the cross section of the MALAL 100, and FIGS. 14B-14C illustrate the formation of the small zone 20 detected via a rapidly changing interference pattern 40 appearing in a standard interferometer.

[0119] If the size of the accidental zone 20 is very small, further measurements can be taken before the adjustment step of Figure 5B to modify the spatial profile of the adjustment illumination 210 so that the combined effect of the accidental zone 20 and the modified adjustment illumination 210 together induces a predetermined adjustment of the optical properties of the LAL 110. In other embodiments, the adjustment illumination 210 can be applied with a spatial profile that simply approximately compensates for the optical effect of the small zone 20. The same process can be performed if the accidental zone 20 is formed after the adjustment step of Figure 5B but before the lock-in step of Figure 5E; in this case, the profile of the lock-in illumination 220 should be adjusted to compensate for the presence of the accidental zone 20.

[0120] Another way to look at the protective ability of the front protective layer 120 is as follows: in some embodiments of the MALAL 100, the absorption modulation time T am The zone formation time T zf It can be made shorter than :T am <T zf In some representative cases, the absorption modulation time (the time it takes for the modulated absorption compound 300 to transition from the low absorption coefficient isomer 300-l to the high absorption coefficient isomer 300-h) can range from 0.1 seconds to 10 seconds, and in some other cases from 0.1 seconds to 1 second, while the LAL110 zone formation time can range from 5 seconds to 100 seconds, and in some other cases from 10 seconds to 50 seconds. Such a front protective layer 120 can effectively prevent zone formation even in the extremely rare case where the modulated absorption compound 300 inadvertently transitions from the high absorption isomer 300-h to the low absorption isomer 300-l, allowing the front protective layer 120 to self-heal before zone formation.

[0121] Finally, FIGS. 15A-15B show a method 400 for adjusting the optical properties of the modulated absorptive light-tuning lens MALAL100, which includes the following steps.

[0122] - Reducing (410) the absorption of the modulatable absorbing compound 300 of the modulatable absorbing front protective layer 120 of the MALAL 100 previously implanted in the eye by a modulatable stimulus 310.

[0123] - Changing (420) the optical properties of the photo-adaptive lens of MALAL 100 by applying the conditioning illumination 210.

[0124] In some embodiments of method 400, reducing absorption (410) includes applying (415) a high-low modulation stimulus 310-htl as a modulation stimulus to transition modulatable absorbing compound 300 from a high absorption conformation 300-h to a low absorption conformation 300-l.

[0125] After the change in optical property (420), the modulatable absorbing compound 300 is transitioned (425) from the low absorbing conformation 300-l to the high absorbing conformation 300-h by applying a low-high modulation stimulus 310-lth as the modulation stimulus 310. In some cases, the high-low modulation stimulus 310-htl includes high-low illumination with light having a narrow band centered at a wavelength in the range of 300-400 nm, and the low-high modulation stimulus 310-lth includes one of low-high illumination with light having a broad band centered at a wavelength in the range of 300-700 nm, ambient illumination, and thermal relaxation.

[0126] While this document contains many specifications, details, and numerical ranges, these specifications, details, and numerical ranges should not be construed as limiting the scope of the invention, but rather as describing features specific to particular embodiments of the invention. Some features described in this document in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features described in the context of a single embodiment can also be implemented in multiple embodiments individually or in any suitable subcombination. Furthermore, while features may be described above as functioning in certain combinations and initially claimed as such, in some cases, one or more features resulting from claimed combinations can be deleted from those combinations, or the claimed combinations can be directed to other subcombinations or variations of subcombinations. Another aspect of the present invention may be as follows. [1] A modulating absorption light adjusting lens (MALAL), a light-adjusting lens that can change optical properties upon modulating illumination, the light-adjusting lens comprising a light-modifiable material; a modulatable absorbing front protective layer comprising a modulatable absorbing compound having absorption properties that can be modulated by a modulating stimulus; MALAL, characterized by comprising: [2] The photomodifiable material comprises a polymer host matrix selected from the group consisting of a silicone-based matrix, an acrylate-based matrix, a collamer, a hybrid silicone-acrylate-based matrix, and a multilayer matrix combining at least two of the above matrices; The MALAL described in [1] above. [3] The photomodifiable material includes at least one of a photoinduced polymerizable monomer and a macromer; The MALAL described in [1] above. [4] The photomodifiable material includes a photoinitiator separate from the macromer or a functional group at the end of the macromer. The MALAL described in [1] above. [5] containing a dispersed ultraviolet absorber, The MALAL described in [1] above. [6] Including haptics extending from the light-adjusting lens; The MALAL described in [1] above. [7] The modulating stimulus is selected from the group consisting of electromagnetic illumination, laser illumination, infrared illumination, ultraviolet illumination, magnetic stimulation, electric field, chemical or thermal stimulation, heat transfer, energy transfer, ultrasound-mediated stimulation, mechanical stimulation, thermal stimulation, and thermal relaxation. The MALAL described in [1] above. [8] The modulating absorbing compound is dispersed in the front surface region of the light accommodating lens to form the modulating absorbing front surface protective layer. The MALAL described in [1] above. [9] The modulating absorption compound is localized in a polymer host matrix in the anterior region of the light accommodating lens. The MALAL described in [8] above.

[10] The modulating absorption compound is localized in the polymer host matrix by one or more bonds to a crosslinker of the polymer host matrix and at least one of the chains of the polymer host matrix. The MALAL described in [9] above.

[11] The one or more bonds that localize the modulable absorption compound include a bond that connects one of carbon and silicon to one selected from the group consisting of carbon, silicon, oxygen, nitrogen, hydrogen, sulfur, and halogen atoms; The MALAL described in

[10] above.

[12] The modulatable absorption compound is one of a long polymer that is mobile relative to the polymer host matrix and interpenetrates the photomodifiable material. The MALAL described in [8] above.

[13] The modulating absorption front protective layer is one of a layer attached on the front surface region of the light accommodating lens and a layer deposited on the front surface region of the light accommodating lens; The MALAL described in [1] above.

[14] The modulating absorbing front protective layer is disposed in front of the light accommodating lens, is at least partially separated from the light accommodating lens, and is optionally held in place by a carrier structure. The MALAL described in [1] above.

[15] The thickness of the modulating absorbing front protective layer is less than one of 50%, 25%, 5%, and 2% of the thickness of the light accommodating lens; The MALAL described in [1] above.

[16] The modulating absorption compound is selected from the group consisting of an azoaromatic compound, a diazene, an azopyrazole, a dienylethene, a fulgide, an azulene, a spiropyran, an ethene aromatic compound, a macromer of one of these compounds, a polymer of these compounds, a composition comprising one of these compounds, a composition comprising one of these compounds as a side chain, a composition comprising one of these compounds as a main chain with side chains, nanoparticles bound to one of these compounds, and one of these compounds dissolved in an ionic fluid. The MALAL described in [1] above.

[17] The azo aromatic compound is one of azobenzene and 4-methoxyazobenzene, the azopyrazole is vinylphenylazopyrazole, and the ethene aromatic compound is stilbene. The MALAL described in

[16] above.

[18] The modulatable absorption compound is selected from the group consisting of a photoswitchable compound, a photoactivatable compound, a photoisomerizable compound, a photochromic compound, a photoconvertible compound, and a switchable chromophore; The MALAL described in [1] above.

[19] The modulatable absorption compound has at least a high absorption conformation and a low absorption conformation; the modulatable absorption compound is capable of transitioning from the high absorption conformation to the low absorption conformation upon absorption of a high-low modulation stimulus; the modulatable absorption compound is capable of transitioning from the low absorption conformation to the high absorption conformation upon absorption of a low-to-high modulation stimulus; The MALAL described in [1] above.

[20] The high-low modulation stimulus includes high-low illumination with light having a band centered on a wavelength in the range of 300 to 400 nm; The low-high modulation stimulus comprises one of low-high illumination with light having a band centered at a wavelength in the range of 400 to 700 nm and thermal relaxation. The MALAL described in

[19] above.

[21] The ratio of the absorption coefficient of the high absorption conformation to the absorption coefficient of the low absorption conformation in a wavelength range of 300 to 400 nm is greater than 2; The MALAL described in

[20] above.

[22] The high absorption conformation of the modulating absorption compound has a lower energy than the low absorption conformation such that, at equilibrium under ambient conditions, in at least one of a solid phase, a dilute solution, and a host matrix-bound state, the ratio of the concentration of the modulating absorption compound in the high absorption conformation to the concentration of the modulating absorption compound in the low absorption conformation is greater than 2. The MALAL described in

[20] above.

[23] The modulatable absorption compound has an absorption of 1 mJ / cm over a wavelength range of 300 nm to 400 nm.2 ~1,000mJ / cm 2 and a chemical composition such that at least 25% of the high absorbing conformation transitions to the low absorbing conformation under high-low illumination with a radiation exposure in the range of The MALAL described in

[20] above.

[24] The modulatable absorption compound has a chemical composition such that the quantum yield of the transition from the high absorption conformation to the low absorption conformation is greater than 0.01. The MALAL described in

[23] above.

[25] The modulatable absorption compound has an absorption of 1 mJ / cm over a wavelength range of 400 nm to 600 nm. 2 ~1,000mJ / cm 2 and a chemical composition such that at least 50% of the low absorbing conformation transitions to the high absorbing conformation under low to high modulation stimulation with radiation exposure in the range of The MALAL described in

[20] above.

[26] The modulatable absorption compound can repeatedly transition from the high absorption conformation to the low absorption conformation and back to the high absorption conformation upon absorption of the high-low modulation stimulus and the low-high modulation stimulus, respectively. The MALAL described in

[19] above.

[27] The modulated absorption front protection layer has a luminance of 3 mW / cm integrated over a wavelength range of 300 nm to 400 nm. 2 Maximum intensity not exceeding 10,000mJ / cm 2 and a further non-modulatable ultraviolet absorbing compound having a chemical composition, extinction coefficient, and thickness sufficient to prevent modulation of the optical properties of said light regulating lens when exposed to a radiation exposure of The MALAL described in [1] above.

[28] A method for adjusting the optical properties of a Modulation Absorption Light Modulating Lens (MALAL), comprising: reducing the absorption of the modulatable absorbing compound in the modulatable absorbing front protective layer of the MALAL previously implanted in the eye by a modulatable stimulus; changing the optical properties of the MALAL light accommodating lens by applying accommodating illumination; A method comprising:

[29] The step of reducing the absorption includes applying a high-low modulation stimulus as a modulation stimulus to transition the modulatably absorbing compound from a high-absorbing conformation to a low-absorbing conformation; after the step of changing the optical property, applying a low-to-high modulation stimulus as the modulation stimulus to transition the modulatable absorbing compound from the low-to-high absorption conformation; The method according to

[28] above.

[30] The high-low modulation stimulus includes high-low illumination with light having a band centered on a wavelength in the range of 300 to 400 nm; The low-high modulation stimulus comprises one of low-high illumination with light having a band centered at a wavelength in the range of 400 to 700 nm and thermal relaxation. The MALAL described in

[29] above. [Explanation of symbols]

[0127] 100 Modulated absorbing light-adjusting lens 110 LAL 111 Photomodifiable materials 120 Modulated absorbing front protective layer 122 Front area 130 Haptic 300 Modulated Absorption Compounds

Claims

1. A modulating absorbing light adjusting lens (MALAL), comprising: a light-adjusting lens that can change optical properties upon modulating illumination, the light-adjusting lens comprising a light-modifiable material; a modulatable absorbing front protective layer comprising a modulatable absorbing compound having absorption properties that can be modulated by a modulating stimulus; MALAL characterized by comprising:

2. the photomodifiable material comprises a polymer host matrix selected from the group consisting of a silicone-based matrix, an acrylate-based matrix, a collamer, a hybrid silicone-acrylate-based matrix, and a multilayer matrix combining at least two of the foregoing matrices; The MALAL of claim 1.

3. the photomodifiable material comprises at least one of a photoinduced polymerizable monomer and a macromer; The MALAL of claim 1.

4. the photomodifiable material includes a photoinitiator separate from the macromer or a functional group at the end of the macromer; The MALAL of claim 3.

5. the light modulating lens further comprises a dispersed ultraviolet absorber; The MALAL of claim 1.

6. a haptic extending from the light accommodating lens; The MALAL of claim 1.

7. The modulating stimulus is selected from the group consisting of electromagnetic illumination, laser illumination, infrared illumination, ultraviolet illumination, magnetic stimulation, electric field, chemical or thermal stimulation, heat transfer, energy transfer, ultrasound-mediated stimulation, mechanical stimulation, thermal stimulation, and thermal relaxation. The MALAL of claim 1.

8. the modulating absorbing compound is dispersed in the front surface region of the light regulating lens to form the modulating absorbing front surface protective layer; The MALAL of claim 1.

9. the modulating absorbing compound is localized in a polymer host matrix in the anterior region of the light regulating lens; The MALAL of claim 8.

10. the modulating absorbing compound is localized in the polymer host matrix by one or more bonds to a crosslinker of the polymer host matrix and at least one of the chains of the polymer host matrix; 10. The MALAL of claim 9.

11. the one or more bonds localizing the modulative absorption compound include a bond connecting one of carbon and silicon to one selected from the group consisting of carbon, silicon, oxygen, nitrogen, hydrogen, sulfur, and halogen atoms; The MALAL of claim 10.

12. the modulatable absorbing compound is one of: mobile with respect to the polymer host matrix and a long polymer that interpenetrates the photomodifiable material; The MALAL of claim 8.

13. the modulating absorbing front protective layer is one of a layer adhered onto the front surface region of the light accommodating lens and a layer deposited onto the front surface region of the light accommodating lens; The MALAL of claim 1.

14. the modulating absorbing front protective layer is disposed in front of the light regulating lens and is at least partially separated from the light regulating lens, and is optionally held in place by a carrier structure; The MALAL of claim 1.

15. the thickness of the modulating absorbing front protective layer is less than one of 50%, 25%, 5% and 2% of the thickness of the light accommodating lens; The MALAL of claim 1.

16. the modulating absorption compound is selected from the group consisting of an azoaromatic compound, a diazene, an azopyrazole, a dienylethene, a fulgide, an azulene, a spiropyran, an ethene aromatic compound, a macromer of one of these compounds, a polymer of these compounds, a composition comprising one of these compounds, a composition comprising one of these compounds as a side chain, a composition comprising one of these compounds as a backbone with side chains, nanoparticles bound to one of these compounds, and one of these compounds dissolved in an ionic fluid; The MALAL of claim 1.

17. the azo aromatic compound is one of azobenzene and 4-methoxyazobenzene, the azopyrazole is vinylphenylazopyrazole, and the ethene aromatic compound is stilbene; 17. The MALAL of claim 16.

18. the modulatable absorption compound is selected from the group consisting of a photoswitchable compound, a photoactivatable compound, a photoisomerisable compound, a photochromic compound, a phototransformable compound and a switchable chromophore; The MALAL of claim 1.

19. the modulably absorbing compound has at least a high absorbing conformation and a low absorbing conformation; the modulatable absorption compound is capable of transitioning from the high absorption conformation to the low absorption conformation upon absorption of a high-low modulation stimulus; the modulatable absorption compound is capable of transitioning from the low absorption conformation to the high absorption conformation upon absorption of a low-to-high modulation stimulus; The MALAL of claim 1.

20. the high-low modulation stimulus comprises high-low illumination with light having a band centered at a wavelength in the range of 300 to 400 nm; the low-high modulation stimulus comprises one of low-high illumination with light having a band centered in a wavelength range of 400-700 nm and thermal relaxation; 20. The MALAL of claim 19.

21. the ratio of the extinction coefficient of the high absorbing conformation to the extinction coefficient of the low absorbing conformation in the wavelength range of 300 to 400 nm is greater than 2; 21. The MALAL of claim 20.

22. the higher absorption conformation of the modulating absorption compound has a lower energy than the lower absorption conformation such that at equilibrium under ambient conditions, in at least one of a solid phase, a dilute solution, and a host matrix bound state, the ratio of the concentration of the modulating absorption compound in the higher absorption conformation to the concentration of the modulating absorption compound in the lower absorption conformation is greater than 2; 21. The MALAL of claim 20.

23. The modulatable absorption compound provides an absorption of 1 mJ / cm over the wavelength range of 300 nm to 400 nm. 2 ~1,000mJ / cm 2 and a chemical composition such that at least 25% of the high absorbing conformation transitions to the low absorbing conformation under high-low illumination with a radiation exposure in the range of 21. The MALAL of claim 20.

24. the modulably absorbing compound has a chemical composition such that the quantum yield of the transition from the high absorbing conformation to the low absorbing conformation is greater than 0.01; 24. The MALAL of claim 23.

25. The modulatable absorption compound provides an absorption of 1 mJ / cm over the wavelength range of 400 nm to 600 nm. 2 ~1,000mJ / cm 2 and a chemical composition such that at least 50% of the low absorbing conformation transitions to the high absorbing conformation under low to high modulation stimulation with radiation exposure in the range of 21. The MALAL of claim 20.

26. the modulatable absorption compound is capable of repeatedly transitioning from the high absorption conformation to the low absorption conformation and back to the high absorption conformation upon absorption of the high-low modulation stimulus and the low-high modulation stimulus, respectively; 20. The MALAL of claim 19.

27. The modulated absorbing front protective layer has an absorbance of 3 mW / cm integrated over the wavelength range of 300 nm to 400 nm. 2 Maximum intensity not exceeding 10,000 mJ / cm 2 and a further non-modulatable ultraviolet absorbing compound having a chemical composition, extinction coefficient, and thickness sufficient to prevent modulation of the optical properties of said light regulating lens when exposed to a radiation exposure of The MALAL of claim 1.

Images