Light tunable intraocular lens with advanced polymerization control

Abstract

A light tunable lens (LAL) that suppresses non-target optical power drift is described. These LALs comprise a polymeric silicone network injected with a removable macromonomer, a non-switchable ultraviolet absorber, a photoinitiator, and a front protective layer comprising a switchable ultraviolet absorber. The LAL is phototunable by shaped illumination that activates a photoinitiator that induces polymerization of the movable macromonomer, thereby changing the optical power of the LAL. The LAL can accommodate an oxygen concentration of 0.5 to 20 ppm; and the ratio of the oxygen concentration multiplied by the oxygen-driven photoinitiator quenching rate to the movable macromonomer concentration multiplied by the photoinitiator-driven polymerization increase rate is greater than 10. Some of these LALs include a non-switchable ultraviolet absorber in the front protective layer; or a free radical scavenger; or a monofunctional or sterically hindered movable macromonomer; or a switchable photoinitiator, or an anchored photoinitiator.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 505,946, filed June 2, 2023, and U.S. Application No. 18 / 678,181, filed May 30, 2024, entitled "Light-tunable intraocular lens with advanced polymerization control," by I. Goldshleger, J. Kondis, V. Piunova, and C. Sandstedt, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This invention relates to light-tunable lenses, and more particularly to advanced control techniques for polymerization processes in these lenses. Background Technology

[0004] Cataract surgery techniques are advancing at an impressive pace. Generations of phacoemulsification platforms and the recently introduced surgical lasers have continuously improved the precision of intraocular lens (IOL) placement and reduced unintended medical outcomes. However, after IOL implantation, the postoperative healing process can cause IOL displacement or tilting in a significant proportion of patients, resulting in reduced visual acuity and deviation from the planned surgical outcome.

[0005] New techniques have recently been developed to correct or mitigate such postoperative IOL displacement or tilting. IOLs can be made from photopolymerizable materials, subsequently transforming them into light-tunable lenses or LALs. Within days after surgery, the implanted LAL can shift and tilt, eventually settling into a postoperative position different from the surgeon's plan, just like all other intraocular lenses or IOLs. However, unlike other IOLs, once LAL settling occurs, a light delivery system (LDD) can be used to illuminate the LAL with an irradiated beam profile that induces photopolymerization within the LAL at a predetermined spatial profile, thereby altering the LAL's refractive properties. This refractive change modulates the LAL's optical properties to compensate for the non-targeted postoperative displacement or tilting. This modulation procedure is followed by a locking procedure, which deactivates all remaining photopolymerizable material.

[0006] In a limited percentage case, the locking procedure may not deactivate all photopolymerizable material. Subsequently, this remaining portion of photopolymerizable material, when exposed to sunlight, can cause additional, undesirable drift in the optical power of the LAL. Therefore, advanced polymerization control techniques are needed to limit or eliminate undesirable optical power drift in the LAL. Summary of the Invention

[0007] Light-adjustable lenses (LALs) that address the above challenges can include different polymer control designs, processes, and techniques, as described below.

[0008] Some light-adjustable lenses (LALs) include: a polymeric silicone network infused with a mobile macromer, a non-switchable ultraviolet absorber, and a photoinitiator; and a front protective layer comprising a switchable ultraviolet absorber; wherein the LAL is light-adjustable by a shaping irradiation that activates the photoinitiator, which induces polymerization of the mobile macromer, thereby changing the optical power of the LAL; the LAL is capable of accommodating oxygen concentrations in the range of 0.5-20 ppm; and the ratio R (R = kq

[02] / ka[MM]) of the oxygen concentration

[02] times the oxygen-driven photoinitiator quenching rate kq to the mobile macromer concentration [MM] times the photoinitiator-driven polymerization addition rate ka is greater than 10.

[0009] In some light-adjustable lenses, the front protective layer comprises a non-switchable ultraviolet absorber.

[0010] In some light-adjustable lenses, the LAL comprises a radical scavenger or antioxidant.

[0011] In some light-adjustable lenses, the mobile macromer is monofunctional.

[0012] In some light-adjustable lenses, the mobile macromer is sterically hindered.

[0013] In some light-adjustable lenses, the photoinitiator is switchable between a protected state and an activatable state.

[0014] In some light-adjustable lenses, the chemical composition, concentration, and reaction rates of the silicone network, mobile macromer, switchable and non-switchable ultraviolet absorbers, and photoinitiator are such that the slope of the time-dependent power adjustment curve increases by a factor of two or more after a t(activation) time, where t(activation) is in the range of 3 seconds-100 seconds, during a light adjustment procedure.

[0015] In some light-adjustable lenses, the photoinitiator is anchored to the polymeric silicone network.

[0016] In some light-adjustable lenses, the photoinitiator is capable of becoming an activated photoinitiator upon absorbing a UV photon; and the activated photoinitiator is capable of activating the mobile macromer by activating an end group of the mobile macromer.

[0017] In some light-tunable lenses, the activated end group of the mobile macromonomer can form a bond with a second mobile macromonomer, thereby activating the end group of the second mobile macromonomer in the process.

[0018] In some light-tunable lenses, the reaction of activated photoinitiators with oxygen produces low-activity photoinitiator derivatives.

[0019] In some light-tunable lenses, the reaction of activated, mobile macromolecular monomers with oxygen produces low-activity compounds; and the LAL includes a free radical scavenger that can react with the low-activity compounds to convert them into inactive compounds. Attached Figure Description

[0020] Figures 1A-F illustrate the light modulation steps in a light-tunable lens (LAL 100).

[0021] Figure 2A -B shows an optically tunable lens (LAL) with a front protective layer and a rear protective layer.

[0022] Figure 3 The main compounds and structures in LAL 100 are shown.

[0023] Figure 4 The steps of photoinduced interaction between a mobile macromolecular monomer and a photoinitiator are shown.

[0024] Figure 5A -C illustrates two pathways for fixing mobile macromolecular monomers.

[0025] Figure 6A -B illustrates the dynamics of oxygen concentration and power changes during UV irradiation.

[0026] Figure 7 The concentrations of oxygen [O2] and photoinitiator radicals [PI*] during and after the UV irradiation process (including conditioning, locking, and possible zone formation) are shown.

[0027] Figure 8 The concentrations of oxygen [O2] and photoinitiator free radicals [PI*] are shown during and after non-targeted UV exposure.

[0028] Figure 9A -B illustrates the reaction kinetics of the free radical scavenger RS ​​125.

[0029] Figure 10A -B summarizes the steps of aggregation and the design methods for aggregation control.

[0030] Figure 11A-B shows the concentrations of oxygen [O2] and XOO* radicals [XOO*] in the absence and presence of the free radical scavenger RS.

[0031] Figure 12 Polymerization using the monofunctional macromonomer MM(1) is shown.

[0032] Figure 13 The absorption properties of switchable and non-switchable UV absorbers are shown. Detailed Implementation

[0033] The central step in cataract surgery is the implantation of an intraocular lens (IOL). Ophthalmologists use sophisticated and time-tested calculations to select an IOL with optimal optical properties and position it with extreme care within the capsule. After implantation, as the scar and incision heal, the IOL settles in the eye, and the eye tissues respond to the surgery and implantation. This typically takes several weeks and often results in displacement and / or tilting of the IOL away from its implantation location. Therefore, despite careful preparation and informed selection by the ophthalmologist, these displacements and tilts can cause the IOL's focus to shift away from the retina, leading to impaired visual acuity in the patient. Traditional IOLs have a fixed shape and optical properties, and therefore patients must live with this deteriorated visual performance, for example, by wearing corrective glasses. Some ophthalmologists perform LASIK surgery to correct these non-targeted displacements. In contrast, if a light-tunable lens, or LAL 100, is implanted in the patient's eye, the ophthalmologist can determine how to adjust the shape of the LAL 100 to compensate for its displacement and tilt once it settles. This adjustment is achieved by irradiating the LAL 100 with a UV beam, and the shape adjustment is achieved by selecting the beam profile of the UV beam.

[0034] Figures 1A-F illustrate that LAL 100 is capable of such shape changes because its silicone polymer network has been infused with (1) photoinitiator molecules, which can be activated by an incoming UV irradiation beam; and (2) mobile macromonomers, which the activated photoinitiator can induce to bond to the polymer network or to each other. Once the mobile macromonomers are bonded to the network, they become immobilized. This creates a chemielectric potential difference for the remaining mobile macromonomers, which drives them to diffuse from the peripheral, higher concentration regions to the central region, where their concentration has been depleted by the photoinduced immobilization polymerization. This diffusion or drift of the mobile macromonomers towards the central irradiated region causes LAL 100 to swell, which in turn alters its optical properties to re-optimize the patient's visual acuity. This chemical property of LAL 100 will be described in more detail later.

[0035] Once the aforementioned regulation has been performed, the remaining photoinitiators and mobile macromolecular monomers are deactivated by a subsequent “lock-in” procedure, in which “lock-in” UV radiation is applied at a sufficiently high intensity to consume all or substantially all of them.

[0036] To ensure that virtually all photoactive compounds are inactivated, two locking procedures are typically performed several days apart. However, requiring patients to return to the clinic twice for locking procedures after the initial implantation and subsequent optical power adjustment places a considerable burden on both patients and physicians. Therefore, altering the chemistry of these light-tunable lenses 100 to reduce the number of required locking procedures from two to one would provide a significant improvement in the overall convenience and acceptability of light-tunable lens technology, effectively bringing its medical benefits to a significantly larger number of patients. Importantly, the modified lens chemistry still ensures that a single locking procedure consumes substantially all of the photoactive compounds and allows the lens to be sufficiently stable to prevent any subsequent non-targeted light-induced drift of the optical properties.

[0037] Because the retina is highly sensitive to UV radiation, the first-generation LAL 100 included UV absorbers distributed throughout their body, as well as a strongly UV-absorbing backing layer. These UV absorbers prevented modulation and locking of UV radiation from damaging the retina. As an additional safety measure, to prevent untargeted optical adjustments caused by UV levels in sunlight during implantation until locking, patients were instructed to wear UV-blocking sunglasses.

[0038] Figure 2A -B indicates the latest upgrade to the LAL 100, which introduces an additional front protective layer 110. Figure 2A This is a top view of these upgraded LAL 100s, which also shows the LAL 100 stabilized in the ocular capsule after implantation by means of a haptic device 100h. Figure 2B This is a side view of the LAL 100, showing the new anterior protective layer 110 and the previous posterior protective layer 120. The anterior protective layer 110 includes a switchable UV absorber that can switch between a strong UV absorption configuration and a weak UV absorption configuration. This switchable anterior protective layer 110 provides good UV protection in its strong absorption configuration to prevent untargeted optical adjustment prior to locking, while it can switch to its weak absorption configuration to allow UV light to enter the LAL 100 during the adjustment and locking procedures. Its chemical properties will be described in detail later. These upgraded lenses have been widely implanted in patients, and after two locking procedures, they have exhibited perfectly satisfactory optical stability, with no perceptible changes in their optical properties.

[0039] In the search for methods to address the chemistry of one-time-locked lenses, laboratory experiments have shown that, in rare cases, one-time-locked lenses can face potential challenges. Some of these challenges are termed “zone formation” and “power drift,” both of which lead to undesirable variations in the optical power of the LAL 100 at times other than during the adjustment or locking procedure. As will be described in detail below, these undesirable variations in optical power can be caused by at least two classes of processes. When the LAL 100 still contains a significant amount of photoinitiator and mobile macromolecular monomers, faster zone formation changes can be induced primarily by the UV component of ambient / natural light between LAL 100 implantation and locking. Zone formation can be caused by relatively short-duration UV exposure, an example being when a patient may inadvertently look into the sun without the necessary sunglasses while exercising outdoors or using a UV tanning machine.

[0040] Power drift (another type of power change process) is primarily driven by chemical reactions that begin with low-intensity ambient UV light, but is sustained by spontaneous chemical reactions (which occur without further UV irradiation). This self-sustaining power drift occurs much more slowly but can last for a long time, even after the first locking process. As described, the new generation LAL 100 features an added switchable front protective layer 110, the primary function of which is protection against zone formation. This front protective layer 110 has the potential to eliminate the need for wearing sunglasses between implantation and locking, a significant advantage. However, this same front protective layer 110 also hinders the consumption of the macromolecular monomers and photoinitiators during the locking process. Therefore, even after the first locking, a certain percentage of the macromolecular monomers and photoinitiators can remain active, and thus sustain the chemical reactions that lead to power drift. Furthermore, the switchable front protective layer 110 and the distributed UV absorbers still allow a very low percentage of UV photons to enter the body of the LAL 100. Some of these UV photons can be absorbed by the remaining activatable photoinitiator in the centrally exposed region. This UV absorption by the activatable photoinitiator can trigger additional self-sustaining chemical reactions, primarily non-targeted polymerization. Both mechanisms contribute to a slow power drift in the optical power of the LAL100. Real-world ambient light exposure experiments using a single-locked lens show that such a power drift is likely to occur on the order of approximately 0.1D–0.2D over several hundred hours following a single lock.

[0041] In response to the aforementioned challenges, this application primarily describes the chemical considerations and designs for suppressing and minimizing this long-term slow power drift in the next-generation LAL 100, with the ultimate goal of producing an optically stable single-locked light-tunable lens.

[0042] Furthermore, it is noteworthy that lens chemicals that reduce prolonged power drift caused by self-sustaining non-targeted polymerization after the first lock can also reduce short-term zone formation before the first lock. Preventing short-term zone formation with such novel lens chemicals will eliminate the need for patients to wear sunglasses until the first lock, and will therefore enhance control over the outcomes, patient comfort, and acceptance of light-tunable lens technology, thus bringing medical benefits to a larger number of patients.

[0043] To further illustrate this, the chemical properties of the light-tunable lens are described in more detail below. LAL 100 is formed from two polymerizable formulations: a silicone lens matrix or network formulation and a photoreactive formulation. Many details of these formulations are described in US 6450642, entitled “Lenses capable of post-fabrication powermodification,” by Jethmalani et al., the entire contents of which are incorporated herein by reference. In some embodiments, the silicone lens matrix may comprise a silicone polymer, such as a vinyl-terminated siloxane copolymer, or more specifically, a divinyl polydimethyldiphenylsiloxane copolymer as shown:

[0044]

[0045] Where n and m can be 2-100, and in some embodiments 2-30. The composition or concentration of this organosilicon copolymer can be 20%-70%, and in some cases 30%-60%.

[0046] Other components of the network formulation can be a wide variety of polyvinyl functional silicone resins. One example is shown here:

[0047]

[0048] Where x and y can be 2-100, and in some embodiments 2-30. The composition of this silicone resin can be 10%-50%, and in some cases 20%-40%.

[0049] These two components can be linked to the silicone lens network 101 using a variety of crosslinking agents, such as XLK 102 (e.g., polyhydrosilane functionalized compounds), and examples are shown here:

[0050]

[0051] The crosslinking agent XLK 102 can comprise 1%-10%, and in some cases 3%-7%. As part of the curing process, this crosslinking agent XLK 102 can be used to link siloxane polymers together with the organosilicon network 101 via a catalyst-assisted hydrosilylation polymerization process. The curing is carried out at low temperatures to ensure that the photoreactive formulation retains its photoreactivity. This polymerization process produces a large, interconnected organosilicon network 101, or matrix, as previously briefly described. This polymer network 101 is fixed due to its large size and the fact that its numerous branches restrict mobility. It forms the framework of LAL100 and largely determines its mechanical and optical properties.

[0052] The photoreactive formulation may include a variety of acrylate-terminated siloxane macromonomers, an example of which is polydimethylsiloxane with methacrylate end groups:

[0053]

[0054] Where n and x can be 2-100, and in some cases 2-30. These macromonomers are often shorter than the aforementioned siloxane copolymers and silicone resins, and are not attached to the silicon network 101, thus being mobile. The composition of these mobile macromonomers can be 20%-50%, and in some cases 30%-40%. Importantly, the methacrylate end groups are photoactivated via their activatable end groups (or endcaps) 103, as further described below. These macromonomers are also affected by the curing process, but only partially. During the curing hydrosilylation process, a portion of them are linked to the crosslinking agent XLK 102 at one of their methacrylate endcaps 103, and thus become self-fixed macromonomers. Meanwhile, the other methacrylate end group 103 of these fixed macromonomers retains its photoactivity. The remaining portion of these macromonomers remains unrestricted by the network 101 and thus remains mobile. They will be referred to as mobile macromonomers 104 or MM 104. The macromonomer linked to the crosslinking agent will be referred to as (a type of) fixed macromonomer 105 or IM 105. The structure of the formed polymerized organosilicon network 101 has IM 105 linked at the crosslinking agent XLK 102. Meanwhile... Figure 3 The image shows MM 104, which remains movable.

[0055] Photoinitiator 106 or PI 106 is a broad category of known photoinitiators. Some embodiments of photoinitiators include x-alkylbenzoins having the following general formula or structure:

[0056]

[0057] Where R 3 It is H, alkyl, aryl, substituted alkyl, or substituted aryl, and R 4 It is H, alkyl, aryl, substituted alkyl, or substituted aryl; R 5 and R 6 It is phenyl or a substituted phenylallyl or allyloxy group. R 3 and R 4 Specific examples of the group include methyl, phenyltrifluoropropyl, ethyl, and cyanopropyl. (From R) 5 and R 6 The phenyl substituents of the group may include alkyl, alkoxy, halogen, alkylaryl, cyanoalkyl, haloalkyl, and N,N-dialkylamino.

[0058] Another photoinitiator 106 that can be used has one or more UV initiators bonded to a short polymer backbone or segment. This photoinitiator 106 has the general formula AB-A1, where A and A1 can be the same or different UV initiators, and B is a short polymer segment comprising 2-28 monomeric structural moieties. Typically, the photoinitiator 106 tends to have the same polymer backbone as the network used for LAL 100. For example, for LAL 100 made of a silicone polymer, the short polymer linking the initiator can also be a silicone polymer. Similarly, in the case where LAL 100 is based on a polyacrylate, the short polymer chain can be a polyacrylate.

[0059] In one embodiment, photoinitiator 106 comprises one or more UV initiators connected to a polysiloxane bridge and having the following general formula:

[0060]

[0061] Where R 7 -R 11 The structural moiety is independently selected from hydrogen, (primary, secondary, tertiary, cyclo)alkyl, aryl, or heteroaryl, and n is an integer from 2 to 28, and at least one of the structural moieties R 7 -R 11 It is a UV initiator. In a preferred embodiment, R 7 -R 11 It is a C1-C10 alkyl or phenyl, and most preferably methyl, but at least one of them may be hydrogen.

[0062] Particularly useful photoinitiators 106 include benzoyl peroxide (left) and benzoin (right):

[0063]

[0064] The incoming UV photons break or cleave the central OO bond in benzoyl peroxide and the central C / C bond in benzoin. A particularly useful photoinitiator 106 is BL4B, which comprises the benzoyl group shown. "L4" encodes a four-fold repeating organosilicon dimethyl unit.

[0065]

[0066] BL4B PI 106 is bifunctional in the sense that it has two photolytically cleavable bonds (shown by two ellipses). Typically, when PI 106 absorbs UV photons, it typically breaks or cleaves into two highly reactive radicals. The probability of this process is called the quantum yield. As shown below, BL4B breaks into a benzoyl group and a group with a carbonyl radical at the end. Each of these radicals has a radical center: an electron in a highly reactive state.

[0067] For these preparations, photoactivated polymerization is described using chemical reaction equations based on specific examples and at the symbol level. Following widely used notation, UV photons will be denoted by hν, which represents their frequency ν multiplied by Planck's constant h. The number "365" next to hν represents the approximate wavelength of the photon (in nanometers), which is most efficient for performing this cleavage. Photons in the 10-20 nm range near 365 nm can also be used. Electrons in a highly reactive state (radical centers) will be denoted by *, and compounds converted into radicals by these electrons will also be denoted by *. The following figure illustrates the process of photocleavage of BL4B photoinitiator 106 into two radicals (step (1)):

[0068] (1)

[0069] Figure 4 The photoactivated polymerization process is illustrated in three steps at the symbol level. Step (1) is the photolysis just described: the incident photon splits PI 106 into two groups. (Equations with "s" will be used for the symbolic representation of the corresponding chemical reactions: Equation (1s) symbolically represents the reaction of Equation (1), etc.):

[0070] PI + hν = 2PI*.(1s)

[0071] Both PI groups are activated in the sense that they possess electrons that are excited to a highly reactive state and thus form free radicals. For simplicity, both will be represented as PI*106*. Figure 4 The unequal dimensions of the two squares in the figure characterize the unequal dimensions of the two groups.

[0072] Step (2) shows that each activated PI*106* group can react with MM 104, which activates MM in the sense that the reaction transfers highly reactive electronic states to the terminal group of MM, thereby converting it into a free radical. The complete reaction interpretation is as follows (step (2)):

[0073] (2)

[0074] In this process, the highly reactive electrons of PI*106* (its radical center) break the double bond between the central carbon atom of the methacrylate end group and the CH2 group. The electrons of the CH2 group form a bond with the radical center of PI*106*, which deactivates it into deactivated PI. d 106d (shown in shaded) and bonded to MM 104. Notably, the same reaction facilitates another electron from the double bond into a highly reactive state, which forms a new radical center on the central carbon. Figure 4 The symbols indicate these processes in step (2). The methacrylate end group 103 of MM 104 (where the double bond has been broken and one of its electrons is promoted to a highly reactive state) will be referred to as “radical X*” or “activated radical X*” or “activated end group 103*”. In the diagram, hollow symbols indicate pre-reactive groups (activated end group 103, PI 106), solid symbols indicate activated groups (activated group X*103*, activated PI*106*), and shaded symbols indicate deactivated groups (deactivated end group (Xd)103d, deactivated PId 106d). The end group 103 converted to radical X* activates MM 104 to activated MM* 104*, where the activated group will sometimes be explicitly shown as MM-X*. The symbolic representation of the above reaction is in the following form (step (2)):

[0075] PI* + MM = MM*-PId ≡ MM-X*-PId(2s)

[0076] On the right, the deactivated PId is shown in the final product, and the identity (≡) on the right simply introduces shorter and longer symbols for the same activated mobile macromonomer, where the activated end group (MM-X*) is explicitly shown or only implied (MM*).

[0077] Figure 4 It is also shown that in step (2), MM 104 is activated to MM-X* 104*, making it ready for polymerization with a second MM 104 in the subsequent step (3) via the following reaction:

[0078]

[0079] This results in the final state of the two MM 104-bond combinations:

[0080]

[0081] This polymerization or bonding step (3) transfers highly reactive electronic states from the first activated MM-X* 104* to the second MM 104. Thus, the polymerization step (3) deactivates the activated radical X* / terminal 103* of the first MM-X* to the deactivated terminal (Xd) 103d, while simultaneously activating the second MM to MM-X* with its own radical center. Figure 4 This transition in step (3) can be symbolically described as:

[0082] MM-X* + MM = MM-MM-X*(3s)

[0083] In a more detailed representation, the activatable end groups are denoted by Xa or 103a, and the deactivated end groups are denoted by Xd or 103d. Therefore, the polymerization step (3) described above can be written in more detail as follows:

[0084] MM-X* + MM-Xa = MM-Xd-X*-MM.(3s')

[0085] These two symbols can be used interchangeably. In the reaction at step (2), the activated photoinitiator PI*106* activates the activatable end group Xa 103a at the fixed macromonomer IM 105 to IM-X*, and then the polymerization step (3) takes the following form:

[0086] MM-Xa + IM-X* = IM-Xd-X*-MM.(3s'')

[0087] In the detailed step (3) above, MM 104 is shown, which has two activatable end groups 103, both of which are activated by PI*106*, and thus have activated free radicals at both ends: X*-MM-X*. For this reason, such MM104 is sometimes referred to as bifunctional. The MM-MM bonding / polymerization reaction in step (3) involves only one of these free radicals. This reaction allows the bifunctional MM to still enter the second polymerization reaction via its other free radical X*103*. Such bifunctional MM104 (which can polymerize at both of its end groups) can rapidly grow multibranched polymer networks, as described below.

[0088] Figure 5A -C illustrates that this 3-step photoinduced bonding / polymerization of two MM 104 molecules tends to immobilize them. Of course, the immobilization of the mobile macromonomer MM 104 is a driving factor for the variation in optical power, as shown in Figure 1. Figure 5AThe first mechanism for this fixation is shown. Recall that LAL 100 has two types of macromonomers: mobile macromonomers MM 104 that can move freely through the network 101, and fixed macromonomers IM 105 that have been connected to and thus fixed by the crosslinking agent XLK 102 of the silicone network 101 during molding / curing. Figure 5A The photoinduced bonding of a movable MM 104 induced by activated PI*106 to an already fixed IM 105 is shown. (Return to Reference) Figure 4 In step (2), activated PI*106* activates the activatable end group 103a of IM 105, converting it to IM*105*. In the subsequent polymerization step (3), the nearby MM 104 can bond to the activated IM*105*. This step (3) deactivates the fixed macromonomer IM 105 to inactivated IM 105d and transfers the radical center to MM 104 to convert it to activated MM* 104*. In the sister reaction, in step (2), activated PI*106* activates MM 104 to MM* 104*, and in the subsequent step (3), MM* 104* can bond to IM 105, which deactivates MM 104 and activates IM 105 to IM*105*. Both processes result in MM 104 bonding to IM 105, and their complex has activated end groups 103*. Bonding to the immobilized macromonomer IM 105 also naturally immobilizes the mobile macromonomer MM 104. This process is commonly referred to as "grafting" because MM 104 is grafted onto the Si polymer network 101. Grafting is induced by UV irradiation to activate PI 106 into PI*106*, which then grafts MM 104 onto the Si polymer network. Therefore, this UV-induced grafting is a major driver of relatively rapid regioforming.

[0089] Figure 5B A second immobilization mechanism is shown: photoinduced bonding of a mobile MM 104 activated by PI*106* to another mobile MM-X* 104*. Figure 4The result of this process is shown to be the deactivation of the first activated MM-X* 104* into MM-Xd104d, while the second activatable MM-Xa 104a becomes newly activated MM-X* 104. This bonding / polymerization step (3) can be repeated again and again without repeated activation by additional photoactivated PI* 106*. This is the aforementioned self-sustaining polymerization process, which maintains its own repetition without repeated absorption of UV photons. This process is sometimes referred to as chain polymerization. Since chain polymerization can repeat itself without activating additional photoinitiator PI 106 besides the initial PI 106 (which initially initiates this cluster of MM 104), it can continue spontaneously in a self-sustaining manner without UV light. However, its rate is lower than that of the initial PI*-induced step (2), because the reactivity or reaction rate of the UV-activated PI*-induced step (2) is significantly faster than that of the chain polymerization.

[0090] Figure 5B It is shown that a single initial photoinduced activation of PI 106 can trigger the formation of a network by increasing the number of MM 104 along the zigzag backbone. Figure 5C An embodiment in which MM 104 is bifunctional is shown, see Equation (3), where side branches can be nucleated by a second photoactivated PI*106*, and additional side branches can be nucleated by additional photoactivated PI*106*. The size of the resulting MM 104 complex clusters or networks increases rapidly, and many complex branches can develop. Due to the increased size of the clusters, the probability of them entanglement with the organosilicon network 101 also increases, thus the mobility of the clusters decreases rapidly. This entanglement of the growing MM 104 clusters into the organosilicon matrix 101 is achieved through mechanical constraint and restriction, rather than the formation of chemical bonds. However, it also effectively immobilizes MM 104. Therefore, Figure 5B This process of -C can be characterized as chain aggregation, which leads to entanglement.

[0091] Equations (2)-(3) and Figure 5A Both the grafting and winding processes of -C lead to the eventual loss of mobility of MM 104, which effectively anchors IM 105. This anchoring induces shape changes in LAL 100, as illustrated in Figure 1. The rapid UV-induced grafting and UV-induced initiation of chain-wound polymerization are mechanisms for rapid region formation. Even in the absence (or minimal presence) of UV irradiation, the subsequent slow but self-sustaining chain-wound polymerization is the primary mechanism for slow power drift. This power drift can be enhanced by the low-intensity UV component of ambient light.

[0092] This document describes methods, techniques, and chemical designs for controlling and reducing these non-targeted polymerization processes that drive grafting and entanglement, primarily to reduce undesirable long-term slow optical power drift, but also potentially to reduce short-term region formation.

[0093] First, we review the processes for terminating these undesirable polymerization mechanisms. Then, we describe implementation schemes for utilizing and controlling these termination processes to suppress and minimize power drift in LAL 100. The first process of terminating chain polymerization occurs when two free radicals X*103* at the ends of their respective MM 104 or IM 105 physically approach each other and deactivate each other, thereby terminating their growth, and are notated as follows:

[0094] X* + X* = XX(4s)

[0095] In more detail the notation:

[0096] MM-X* + MM-X* = MM-XX-MM.(4s')

[0097] Several other processes that limit or influence the rate of non-targeted polymerization are related to oxygen, which is inevitably present in the aqueous environment of the implanted LAL100. In the aqueous phase of the eye, the O2 concentration is approximately 0.5 ppm, significantly lower than 6 ppm (a typical concentration in water exposed to atmospheric conditions). The O2 concentration within the LAL 100 (hereinafter referred to as [O2]) is in equilibrium with the O2 in its surrounding aqueous environment. Notably, because the oxygen solubility in the LAL 100 is approximately 8 times that in water, the [O2] within the LAL 100 in equilibrium with the 0.5 ppm in the aqueous phase is approximately 8 times, or approximately 4 ppm, as further described below. This oxygen concentration [O2] is maintained by the body's homeostasis: if a chemical reaction begins to deplete the oxygen in the LAL 100, the surrounding aqueous phase will tend to restore this concentration fairly quickly. As described below, even at these low concentrations, oxygen plays a significant role in the chemical properties of the LAL 100. Therefore, controlling the oxygen content of the LAL 100 can be used to suppress power drift.

[0098] In a particularly relevant instance, the activated photoinitiator PI*106* reacts with oxygen, rather than with the activated mobile macromonomer MM 104. This reaction yields the less reactive PI derivative PI-OO, denoted as:

[0099] PI* + O2 = PI-OO(5s)

[0100] This example of a symbolic response (5s) is clearly shown as follows:

[0101] (5)

[0102] In this context, following convention, the remaining portions of the PI molecule are indicated by R' and R”. Another example is the aforementioned benzoin PI106, where the reaction of the activated PI*106* radical with oxygen ultimately produces benzoic acid:

[0103]

[0104] These less reactive PI derivatives (e.g., oxidized PI-OO) are far less reactive than activated PI*106*, hence PI-OO is not marked with an asterisk (*). It is evident that the activated photoinitiator PI*106* consumes a significant amount of PI*106* through its reaction with oxygen, thus advantageously reducing non-targeted polymerization. For completeness, it is noted that less reactive PI-OO can still induce the PI-OO + MM = IM-X* reaction, but at a much slower rate than reactions involving PI*106*. Informally, the less reactive PI derivative PI-OO (and its variants such as PI-OH) will be referred to as a "zombie photoinitiator."

[0105] Due to process (5), the presence of oxygen is detrimental to the conditioning process because it reduces the concentration of the photoinitiator used to induce LAL conditioning. However, the presence of oxygen is very helpful in stabilizing LAL 100 against long-term power drift, especially after lock-in, as it deactivates potential sources of non-targeted polymerization (including power drift). Notably, the reaction rate of process (2), PI*+MM=IM-X*, is k1=10. 2 – 10 4 L / mol*s, while the reaction rate of process (5), PI*+O2= PI-OO reaction, is approximately k2= 10 6 -10 8 L / mol*s. The ratio of these two reaction rates is estimated to be k1 / k2 = 10. -2 -10 -4 In some implementation schemes, it is 10 -3The rates are on the order of magnitude. These rates, of course, depend on various factors such as temperature and concentration. Therefore, as long as oxygen is present in LAL 100, most of the free radicals PI*106* will react with oxygen, rather than with the mobile macromonomer MM 104. Therefore, it is wise to include an appropriate concentration of oxygen in LAL 100 as an effective way to control the polymerization, as it greatly reduces or even stops untargeted photopolymerization that would lead to regioforming or power drift. It will be described below that simply increasing [O2] during fabrication is not expected to be beneficial, as the [O2] is expected to return to equilibrium with the corresponding [O2] in the aqueous phase. Therefore, the implementation emphasizes physicochemical design to increase the oxygen content of LAL 100. One example is changing the oxygen solubility in LAL 100 mentioned above.

[0106] Figure 6A -B illustrates one of the results of the above process: when the conditioning or locking process, or even the formation of a non-targeted region, begins, there is an initial period during which the UV radiation has been incident on the LAL 100, but only minimal or no power change occurs. This is because most of the photoinitiator molecules PI 106, even when activated by UV photons, are subsequently consumed by the oxygen present in the LAL 100 through a rapid and primary step (5): PI* + O2 = PI-OO. Figure 6A The temporal evolution of the spatial distribution of radius-dependent oxygen concentration [O2](r) during this initial period is shown when LAL 100 is exposed to UV irradiation, as oxygen is consumed and depleted. The polymerization rate of MM104 remains at a minimum as long as a finite concentration of oxygen [O2](r) exists in the irradiated region. Once oxygen is completely consumed and depleted by process (5) at t(activation), as shown by the outermost [O2](r) concentration curve, polymerization and the accompanying power change begin. Figure 6B The dynamic delay of the power change ΔP(t) of LAL 100 is qualitatively shown. Figure 6BIt is shown that during the light regulation process, the slope of the power change curve ΔP(t) is initially low because oxygen inhibits the photoinduced polymerization, even though it is consumed by process (5). Once substantially all of the oxygen is consumed within time t (activation), the photopolymerization is no longer inhibited by oxygen, and thus the slope of the power change curve ΔP(t) increases significantly. In an embodiment, the chemical composition, concentration, and reaction rate of the silicone network 101, the mobile macromonomer MM 104, the switchable and non-switchable ultraviolet absorbers, and the photoinitiator PI 106 are such that during the light regulation process, when oxygen is almost completely consumed in the irradiation area, the slope of this time-dependent power regulation curve can increase to two or more times after the t (activation) time. In some embodiments herein, t (activation) can be 3 seconds - 100 seconds; in other cases, it is 5 seconds - 50 seconds. In cases where the slope of the ΔP(t) curve changes significantly, the slope averaged over a period of 5 - 10 seconds after t (activation) can be at least 2 times the average slope over the period of 0 - t (activation). In some cases, this slope ratio can be greater than 1.5. Return reference Figure 6A , in some embodiments, the oxygen concentration [O2] at the center of the LAL 100 decreases by more than 50% during the t (activation) time. In some other LALs 100, the oxygen concentration [O2] at the center of the LAL 100 decreases by more than 90% during the t (activation) time.

[0107] In terms of kinetics, the above reaction involving PI can be represented by the following rate equation:

[0108] d[PI*] / dt = +αI(UV)[PI] – k1[MM][PI*] – k2[O2][PI*].(6)

[0109] Here I(UV) represents the intensity of the incoming UV irradiation, α is the efficiency constant, [PI*], [PI], and [MM] represent the concentrations of the compounds PI*, PI, and MM; and k1 and k2 are the reaction rates of processes (2) and (5) introduced above. As described above, in a characteristic embodiment, k1 << k2, while [O2] is ~4 ppm, and [MM] = 10 - 50 wt%, and in some embodiments, it is 20 - 30 wt%. The ratio of the total rates (including concentrations) of the two processes consuming PI* is represented by R = k2[O2] / k1[MM]. This can also be considered as the ratio of the PI quenching rate Rq = kq[X*][O2] to the increasing rate Ra = ka*[X*][MM], whereby R = Rq / Ra = kq[O2]) / ka[MM], as described above, which determines that kq = k2 and ka = k1.

[0110] The implementation scheme can reduce undesirable power drift by having a high R ratio, which means that most of the activated PI*106* is quenched by oxygen, rather than activating MM 104 into the radical MM-X*104*. In some embodiments, R can be in the range of 1-1000, in some embodiments in the range of 1-100, and in others in the range of 1-10. In such LAL 100 where R >> 1, most of the PI* radicals 106* are neutralized / consumed by oxygen, thereby reducing undesirable polymerization of the mobile macromonomer MM 104. In contrast, in LAL 100 where R is close to 1 or even less than 1, most of the PI* radicals 106* actively promote the polymerization of the mobile macromonomer MM 104, which induces uncontrolled polymerization and power drift. Therefore, producing LAL 100 with an R ratio much greater than 1 is another effective method for polymerization control and power drift prevention.

[0111] Another important oxygen-related reaction that reduces chain polymerization is that the free radical X* driving the polymerization also reacts with oxygen, rather than reacting with other mobile macromonomers MM 104. This reaction converts the highly reactive free radical X* into a less reactive XOO* compound, denoted as:

[0112] X* + O2 = XOO*.(7s)

[0113] Or, more specifically:

[0114] MM-X* + O2 = MM-XOO*.(7s')

[0115] The low-reactivity free radical XOO* is typically a peroxide (or peroxy group). Because XOO* compounds are much less reactive than free radical X*, this process largely deactivates the free radical X*. While the ability of these low-reactivity XOO* compounds to initiate subsequent chain polymerization is suppressed, it remains non-zero, as described below.

[0116] Using these preparations (5)-(7), the rate equation for oxygen concentration can be written as follows:

[0117] d[O2] / dt = β([Oeq]-[O2])– k2[O2][PI*] – k3[O2][X*].(8)

[0118] This process evolves spatially via diffusion. Therefore, if spatial correlation is explicitly represented, then:

[0119]

[0120] This equation requires a solution with appropriate boundary conditions, particularly [Oeq] (equilibrium oxygen concentration of LAL 100 in aqueous phase equilibrium with the eye) at the boundary of [O2] fixed at LAL 100. β is a constant representing the rate of the oxygen equilibrium process, and k3 is the reaction rate of process (7). There are corresponding rate equations for [X*], [MM], and the fixed concentration of the macromonomer [IM], which will not be described in detail here.

[0121] Next, the dynamics of [O2], indicated by equations (5)-(9), which are coupled to similar equations for [X*] and [MM], will be described before, during and after the regulation or locking procedure. Figure 7 The concentrations of activated photoinitiator radicals PI*106* [PI*] and oxygen [O2] in LAL 100 are shown. The conditioning or locking procedure begins at t(start) by applying a UV irradiation beam and ends at t(end) by turning off the UV beam. Before the UV beam is applied, oxygen is present at a concentration [Oeq], which is in aqueous phase equilibrium with the eye. Similarly, in the absence of an incident UV beam, there are no activated PI* radicals before t(start), so [PI*] is negligible. Once the UV beam is applied at t(start), PI*106* radicals are generated by UV photons via process (1) or step (1). The fastest process involving activated PI* radicals 106* is process (5), where PI* is consumed by oxygen. Therefore, most of the UV-activated PI*106* is rapidly consumed by process (5). Therefore, after the UV beam is switched on at t(start), [O2] decreases rapidly from [Oeq], while the [PI–OO] concentration (not shown) increases accordingly, and the negligible [PI*] remains at a minimum, as shown. In this process, the decrease in [O2] inhibits the ratio R from reaching its high initial value. This causes the PI* radical 106* to be consumed less and less through reaction with oxygen and more and more through polymerization of the mobile macromonomer MM 104.

[0122] Once the oxygen concentration [O2] reaches approximately zero at t(activation), the PI* radicals 106* cease to be rapidly consumed by oxygen, and thus from t(activation), UV irradiation begins to rapidly increase [PI*], as shown. After t(activation), the PI* 106* radicals primarily induce the polymerization and fixation of the mobile macromonomer MM 104, which induces the modulation of the optical power of LAL 100. [PI*] flattens at a dynamic equilibrium value determined by the balance between the PI* 106* generated by the UV beam and the PI* 106* consumed by the polymerization of MM 104. Formally, the right-hand side of equation (6) is set to 0.

[0123] Finally, when the UV beam is turned off at t(end), according to equation (6), the PI*106* radical concentration [PI*] begins to decrease, and according to equations (8)-(9), the oxygen concentration [O2] climbs back to its equilibrium value [Oeq]. The typical duration of such a regulation or lockout procedure |t(end)-t(start)| is 20-200 seconds; in some implementations it is 30-100 seconds. Figure 7 The figure summarizes the central role of oxygen in influencing the PI*106* concentration [PI*] at each stage of the UV irradiation process. This summary provides a useful background for analyzing and controlling the power drift caused by the reactions of MM 104, PI*106*, and oxygen, primarily over a long period after t (end).

[0124] Although in name Figure 7 The process of light conditioning by intentionally applying a UV beam is illustrated, but it is relevant to non-targeted UV-induced zone formation processes and the UV-induced portion of power drift processes. Zone formation involves UV irradiation at an intensity lower than that used in the conditioning or locking procedure, for example, when a patient is inadvertently exposed to sunlight without wearing the required sunglasses before locking. If this inadvertent exposure persists long enough, the O concentration [O2] can decrease to a sufficiently low level that PI* production begins to accelerate (as occurs after t (activation) in Figures 6-7) and induces polymerization of MM 104, which alters the shape of LAL 100 in the irradiated area. As previously stated, LAL 100 with the pre-protective layer 110 minimizes and typically eliminates the opportunity for such zone formation.

[0125] Figure 8 The diagram shows that under weak ambient UV irradiation, UV activation processes (1) and (5) reach a dynamic equilibrium with a very small but non-zero PI* radical concentration [PI*]. This [PI*] concentration is so small that the UV light is insufficient to reduce [O2] to zero, so most of the activated PI*106* reacts with oxygen and is converted into the zombie photoinitiator PI-OO. Moreover, as shown, this very low but non-zero [PI*] can induce undesirable polymerization and thus increase the power drift ΔP(t) over hundreds of hours. It is clear from this specification that LAL 100, with its chemical composition that accommodates more oxygen, will have a lower equilibrium [PI*] and therefore a slower UV-induced power drift.

[0126] The above specification relates to the UV-induced component of power drift. Typically, a large portion of this power drift is caused by chain polymerization, which can be initiated by UV absorption but continues spontaneously in a self-sustaining manner even without UV irradiation. The role of oxygen in controlling and managing UV-induced polymerization has been described; this specification now turns to its role in controlling chain polymerization. Oxygen also limits and inhibits this polymerization process through process (7), which converts free radicals or activated end groups X*103* into much less reactive XOO* groups, such as peroxy groups. Therefore, an effective control design to inhibit non-targeted polymerization in LAL 100 is to introduce oxygen into LAL 100, which reacts with the X* free radicals 103* (activated mobile macromonomers MM-X*104*) via process (7) and converts them into weakly reactive free radicals XOO* or MM-XOO*.

[0127] However, the reactivity of this low-reactivity free radical XOO* is still not zero, so it can still drive slower power drift over hundreds of hours. Therefore, Figure 9A -B illustrates some embodiments of LAL 100 that control and reduce this non-targeted polymerization by including the radical scavenger RS ​​125 to further deactivate these oxidized, low-activity radicals XOO*, as denoted by:

[0128] RS + XOO* = XOOd (10s)

[0129] Here, XOOd represents the deactivated XOO* group that has reacted with the free radical scavenger RS ​​125. More specifically:

[0130] RS + MM-XOO* = MM-XOOd (10s')

[0131] Potential examples of such free radical scavengers as RS 125 are tocopherol or vitamin E, having the following formula:

[0132]

[0133] The free radical scavenger RS ​​125 can be in different α, β, γ, and δ forms of tocopherol. The O* of XOO* reacts with the OH at the terminal group of the tocopherol, and this electron exchange neutralizes the O* radical center, thereby converting XOO* into an inactive group. Other free radical scavengers include ascorbate, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), or 2,6-di-tert-butyl-4-methoxyphenol. Generally, many types of free radical scavengers are known. A common property of many of them is that they are proton donors, which preferably react with peroxide radicals.

[0134] The above photoactivated polymerization steps (1)-(3) and polymerization control design process (4)-(10) are comprehensively summarized in Figure 10A -B. The numbers in the circles indicate the labels for the steps or processes described. The boxes around the chemical formulas (e.g., PI-OO and MM-Xd-XOOd-MM) indicate that the polymerization control design aims to deactivate these compounds so that they do not participate in further polymerization. The pentagons around O2 and the free radical scavenger RS ​​125 indicate that they are important reagents used in the polymerization control design. Figure 10A -B shows both immobilization via chain polymerization and immobilization via grafting reaction. Figure 10A Using detailed chemical notation, it clearly shows the terminal group X103 of MM 104 and IM 105 in their three states: Xa represents an activated X, X* represents an already activated X, and Xd represents an inactivated X, while Figure 10B Using the simplest notation, MMa represents a mobile macromonomer with an activated terminal group Xa103a, MM* represents a mobile macromonomer with an activated terminal group X*103*, and MMd represents a mobile macromonomer with an inactivated terminal group Xd103d. These two notations are provided as alternative, similar explanations for the same chemical pathway.

[0135] Returning to the polymerization control process (10), some LAL 100s employ a control design that introduces the radical scavenger RS ​​125 into the LAL 100, which reacts with the low-activity radical XOO* and further deactivates them into the nearly inactive group XOOd via process (10). Advantageously, the reaction rate k(RS–XOO*) of tocopherol with the low-activity XOO* / peroxy radical is fast, while its reaction rate k(RS–PI*) with the activated PI*106* is slow. Thus, tocopherol does not substantially slow down the regulation and locking process dependent on the PI*106* radical, while it very effectively achieves the inhibition of non-targeted chain polymerization via process (10), which has been substantially inhibited by oxygen via process (7). Specifically, Figure 9A This demonstrates how the free radical scavenger RS ​​125 inactivates the still moderately active radical center of the low-activity free radical XOO*, and... Figure 9B It is shown that after locking is complete, the polymerization and the corresponding power shift ΔP(t) are suppressed as long as both oxygen and RS 125 tocopherol are present, until all RS 125 tocopherol is consumed.

[0136] Under normal circumstances, the UV component of ambient light experienced by patients from sunlight or indoor exposure reduces the PI concentration [PI] of LAL 100 to zero within a certain time range (e.g., 100-1000 hours) by activating PI106 into PI*106* (which is then consumed by oxygen or by the polymerization process). In some typical cases, this time can be in the range of 300-500 hours. This time can be referred to as the drift-active time. During this drift-active time, essentially all of PI 106 is consumed by the UV component of ambient light. Therefore, polymerization control designs and processes to protect against PI-driven power drift only need to be effective within this drift-active time of several hundred hours, rather than over the decades-long lifespan of LAL 100. Therefore, polymerization control designs and processes that can effectively suppress the main mechanisms of power drift in LAL 100 include the following. (1) Prepare LAL 100 containing sufficient oxygen to deactivate the photoinitiator PI 106 and reduce their activity by converting the free radicals X*103* of the mobile macromonomer 104 and the fixed macromonomer 105 into low-activity free radicals XOO*. Since the [O2] in LAL 100 is in equilibrium with the aqueous phase, an indirect method is required to achieve this. (2) Prepare LAL 100 containing sufficient free radical scavenger RS ​​125 to extensively deactivate the low-activity free radicals XOO* during the drift-active time. The details of the polymerization control design and process for these categories are further detailed below.

[0137] Figure 11A -B provides some details about the free radical scavenger RS ​​125. Figure 8 The influence of power drift kinetics. Figure 11AThis demonstrates that, in the absence of the radical scavenger RS ​​125, when LAL 100 is exposed to some low-intensity / ambient UV radiation, UV photons begin to activate PI*106* radicals via process (1) / step (1). The process of PI*106* generation is constrained by process (5), in which oxygen converts PI*106* radicals into the much less reactive PI-OO zombie photoinitiator. These competing processes (1) and (5) set a dynamic equilibrium [PI*] that depends on [O2], as shown. Process (5) also consumes oxygen and therefore tends to decrease [O2], while the aqueous phase equilibrium to [Oeq] via process (8) tends to increase [O2]. These two competing processes set a dynamic equilibrium [O2] concentration, as shown. And since [O2] converges to a fixed value, the concentration [PI*] also converges to a fixed value, as shown. These fixed concentrations of [O2] and [PI*] are maintained until all PI 106 is consumed, at which point [PI*] returns to its initial near-zero value, and [O2] also returns to its initial value, equilibrating with the aqueous phase. These photoactivated PI*106* induce a slow power drift in LAL 100, as... Figure 8 As shown, the oxygen-generated PI-OO zombie photoinitiator has minimal residual reactivity and therefore does not increase the power drift.

[0138] Figure 11A -B explains that, in conjunction with the above, oxygen converts a portion of the activated end groups X*103* into less reactive XOO* radicals through process (7). The resulting XOO* radicals induce further polymerization and are therefore another driving factor for the power shift ΔP(t). Figure 11A It was shown that as long as PI*106* free radicals are generated by ambient UV irradiation, the concentration of these XOO* free radicals increases over time.

[0139] XOO* radicals can be additionally generated through chain polymerization of PI* radicals 106* without involving UV generation, followed by an oxygen-driven process (7). This process can continue even after locking, because locking primarily polymerizes MM 104 in the central region, and therefore residual MM104 with full-intensity locking beam unreached can exist on the periphery of LAL 100, which can then drift very slowly to the central region of LAL 100 and continue chain polymerization and XOO* generation. Thus, low concentrations of active radicals [XOO*] can still grow and cause a slow power drift of a small percentage program in LAL 100 over hundreds of hours, even after locking, as... Figure 11A As shown.

[0140] Figure 11BSome polymerization control methods are shown that suppress even this residual power drift by utilizing process (10), in which the radical scavenger RS ​​125 deactivates the less reactive XOO* groups. As shown, process (10) suppresses the generation of XOO* groups until all RS 125 is consumed and [RS] reaches zero. When the polymerization control design adds RS 125 in incremental increments, the rise in [XOO*] concentration is delayed, and its kinetic equilibrium value (approximately its plateau value) is reduced. In some cases, even the growth rate of [XOO*] (its slope) is reduced by the introduction of RS 125. Of course, the reduction and control of [XOO*] concentration over time also consumes the radical scavenger RS ​​125, and therefore its concentration [RS] decreases over time, as shown.

[0141] Next, we will discuss the different processes involved in UV absorbers. Figure 2A -B indicates that the recent upgrade of LAL 100 introduced an additional front protective layer 110. Figure 2A This is a top view of LAL 100. Figure 2B This is a side view of LAL 100, showing the front protective layer 110 and the optional, generally useful rear protective layer 120. The front protective layer 110 typically includes a switchable UV absorber that can be switched between a strong UV absorption configuration and a weak UV absorption configuration.

[0142] An embodiment of the switchable UV absorber is azobenzene, which is known to alter its absorption properties upon photostimulation. Azobenzene is in the general form RN=N-R', one of the simplest examples of the group of compounds known as azo compounds, where R and R' can be aryl or alkyl or the group thereof. Azobenzene is known to have two conformations, differing in the bond angle between the N=N double bond and one of the two benzene rings. The "trans" conformation exhibits high absorption in the UV spectrum, peaking in the 360-370 nm wavelength range, where such absorption involves π-to-π* electronic transitions. Similar absorption peaks are also present in various functionalized azobenzenes. UV light at a wavelength of approximately 365 nm can be used as a high-to-low modulation stimulus 310-htl to convert azobenzene from its high-absorption isomer 300-h with the trans conformation to its low-absorption isomer 300-I with the cis conformation. As shown, the cis conformation has a much lower absorption at a wavelength of approximately 365 nm. Therefore, azobenzene is an embodiment of the switchable UV absorber of the preprotective layer 110, which largely blocks incoming UV rays when in its trans conformation, but can be switched to a low-absorption cis conformation to allow modulated radiation to pass through to LAL 100. For completeness, it may be mentioned that azobenzene-based compounds may have additional conformations.

[0143] Besides azobenzene, many other embodiments of switchable UV absorbers exist. These switchable UV absorbers may be azo-aromatic compounds, diazoxides, azo-pyrazoles, dienylethylene, fentanyl anhydride, azulene, spiropyran, ethylene-aromatic compounds, macromonomers of one of these compounds, polymers of these compounds, compositions containing one of these compounds, compositions containing one of these compounds as a side chain, compositions containing one of these compounds as a main chain with a side chain, nanoparticles bonded to one of these compounds; and one of these compounds dissolved in an ionic fluid. The switchable UV absorber may also be a polymer in which any of the compounds just listed are incorporated into the polymer network itself, so that it need not be incorporated as a side chain. Some such compounds may include polymers that bend in response to light. A broad list of embodiments of the switchable UV absorbers continues below in this specification.

[0144] As mentioned above, the azo-aromatic compound may be, for example, an azobenzene exhibiting the following conformational changes:

[0145]

[0146] In other embodiments of the switchable UV absorber, the azo-aromatic compound may be 4-methoxyazobenzene:

[0147]

[0148] The switchable UV absorber may also be indazole, allylated azobenzene with different spacers, or another form of phenylazopyrazole, as shown:

[0149]

[0150]

[0151] In yet other embodiments, the azo-pyrazole may be vinylphenyl azo-pyrazole VPAP:

[0152]

[0153] Finally, in some embodiments, the ethylene-aromatic compound may be bismuth:

[0154]

[0155] Such a switchable absorber implementation is described in great detail in co-owned U.S. Patent Application 16 / 658142 entitled “LightAdjustable Intraocular Lens with a modulable absorption front protection layer” by Goldshleger et al., the entire contents of which are incorporated herein by reference. Under ambient light, these switchable absorbers absorb UV light very effectively. However, when irradiated with a high dose of UV light, the internal dynamic equilibrium between the two (trans and cis) conformations of the VPAP molecule shifts, and the front protection layer 110 becomes partially transparent to UV. This change opens the door to modulating the UV beam into the lens body and triggering the aforementioned modulating effect. Once the modulating radiation is complete and the UV beam is turned off, this front protection layer 110 switches back to strong UV absorption. Through this absorption-switching mechanism, this VPAP front protection layer 110 protects the LAL 100 from partial non-targeted modulation from still-active, mobile macromolecular monomers from implantation to locking.

[0156] Switching between the strong UV absorption configuration and the weak UV absorption configuration can cause the structure of the UV absorber to degrade in a small percentage of these switching events. Furthermore, these back-and-forth switching events occur while the system remains stationary. Therefore, a half-life τ(sUV) can be assigned to the switched UV absorber, representing the number of switching events after which 50% of the switchable UV absorber's structure will degrade and lose its switching capability. This half-life τ(sUV) is based on the number of switching events in which the switchable UV absorber can survive, multiplied by the characteristic time between switches. This switching time depends on temperature and chemical parameters. LAL 100, with its switchable UV absorber exhibiting faster structural degradation, loses its UV protection from the pre-protective layer 110 more quickly. Since lock-in typically occurs 15–30 days post-implantation, and UV exposure is typically less than 10 hours per day, implementations of switchable UV absorbers with a half-life τ(sUV) exceeding 200 hours in the implantation environment are advantageous. Some implementations of switchable UV absorbers can have a half-life τ(sUV) of over 400 hours in the implantation environment.

[0157] The same degradation process can also be reflected by the number of switching events. Depending on their specific chemical composition, switching UV absorber molecules begin to show an increased degree of degradation after a number of switching events, which can range from 50,000 to 500,000, and in some cases 100,000 to 200,000.

[0158] Switching UV absorbers can also lead to degradation, as activated PI* 106* or XOO* molecules migrate into the anterior protective layer 110. Furthermore, after PI 106 is consumed in the anterior central region, PI 106 can migrate from the periphery of the lens or any other region into this anterior central region.

[0159] Next, several aggregation control designs will be described that control and suppress unwanted and uncontrolled aggregation, thereby reducing unwanted power drift in the LAL 100. Implementations of the LAL 100 may combine more than one of the listed aggregation control designs to achieve amplified benefits and advantages.

[0160] (1) One of the widely accepted design principles for polymer control is to produce LAL 100 capable of holding the highest possible concentration of oxygen. Some LAL 100s can hold oxygen concentrations of 0.5–50 ppm. Others can hold oxygen concentrations of 0.5–20 ppm, 4–20 ppm, or 6–20 ppm. The initial oxygen concentration of the LAL 100 is expected to equilibrate with the 0.5 ppm oxygen concentration in the aqueous phase of the eye after implantation. Therefore, LAL 100s need to have chemical and physical properties that allow them to maintain a high oxygen concentration even after equilibration with the aqueous phase. As previously mentioned, one design principle is that LAL 100s with a high R = k2[O2] / k1[MM] ratio can retain excess oxygen, thereby more effectively suppressing unwanted power drift. In the previous equivalent representation, R can also be expressed as the product of oxygen concentration [O2] multiplied by oxygen-driven photoinitiator quenching rate kq (referred to as k1 above), and then divided by the product of mobile macromonomer concentration [MM] multiplied by photoinitiator-driven polymerization increase rate ka (referred to as k2 above): R = kq[O2] / ka[MM].

[0161] In some implementations, R can be greater than 10, 100, or 1000. In organosilicon-based compounds of LAL 100 in equilibrium with an aqueous phase having a certain oxygen partial pressure, the oxygen concentration is given by the product of pressure and oxygen solubility. This solubility is in turn given by oxygen permeability divided by diffusivity. Since the oxygen concentration in the aqueous phase cannot be comfortably altered, the polymerization control design aims to advantageously adjust the solubility or diffusivity of LAL.

[0162] In typical organosilicones, the oxygen permeability due to diffusion is 500-800 "barrers" (non-SI units). In SI units, this permeability is given in mol / (m*s*Pa), and 1 barrer = 3.35*10 -16mol / (m*s*Pa). In existing embodiments of LAL 100, the oxygen permeability is less than 100-200 barrer. Therefore, the chemical design of LAL 100 can be improved by increasing their oxygen permeability and thus solubility, while potentially reducing oxygen diffusivity towards conventional organosilicon performance levels. LAL 100 with such a chemical design will have an increased oxygen concentration [O2] and therefore a reduced power drift. Thus, some LAL 100s may have a specific chemical composition such that the oxygen permeability, solubility, and diffusivity allow for an oxygen concentration of 4-20 ppm, and in some cases 6-20 ppm.

[0163] Another way to capture these aggregate designs is by using equilibrium equations:

[0164] [O2] LAL =(S LAL / S aq [O2] aq (11)

[0165] Among them, [O2] LAL and [O2] aq It refers to the LAL and oxygen concentration in the aqueous phase, while S... LAL and S aq This refers to the solubility in LAL and aqueous phases. In some specialty silicones such as PDMS, the ratio S... LAL / S aq It is approximately 8. This makes it possible even in the aqueous phase [O2] aq It is only about 0.5 ppm, while in LAL it can reach about 4 ppm [O2]. LAL This becomes possible. Some aggregation control designs further enhance this [O2] by doing so as follows. LAL At least one of the polymeric organosilicon network 101 and the mobile macromolecular monomer MM 104 includes at least one of fluorine and fluorine-containing functional groups. Therefore, in some LAL 100s, the ratio S LAL / S aq It can be greater than 5, and in some implementations it can be greater than 10.

[0166] (2) In some LAL 100s, the R ratio can be increased not only by increasing the oxygen concentration [O2], but also by decreasing the reaction rate of k1 (or kq) in the denominator characterizing the polymerization process. The methacrylate end groups of the mobile macromonomer MM can be described by the following formula:

[0167]

[0168] In some LAL 100s, the CH3 side group on the penultimate carbon atom can be replaced by a longer group or chain. In other LAL 100s, one or two hydrogens can be replaced by a CH3 or longer side chain. More generally, the terminal group 103 of the mobile macromonomer MM104 may include a side chain longer than the CH3 methyl group. Such MM 104s have a slower polymerization rate increase k1 (or ka), and therefore a favorable higher R ratio.

[0169] (3) Some LAL 100s may include free radical scavengers (RS) or antioxidants to inhibit unwanted polymerization. In some LAL 100s, the RS concentration [RS] may be 5-1000 ppm, in some embodiments 10-500 ppm, and in still other embodiments 50-200 ppm. One class of antioxidant free radical scavengers is tocopherol or vitamin E. Notably, LAL 100s with elevated [O2] and [RS] concentrations have been found to exhibit a 50% reduction in power drift. Such a 50% reduction can be achieved, for example, in LAL 100s with [O2] concentrations of 5-10 ppm and tocopherol concentrations of 100-200 ppm.

[0170] (4) Figure 12 In some embodiments, power drift can be suppressed through different polymer control designs. In some embodiments of LAL 100, the underlying silicon polymer network can be infused with a mobile macromonomer MM, which can be activated only at one end. In some embodiments, only one end group of the mobile macromonomer MM 104(1) is an acrylate. Such macromonomers can be referred to as monofunctional macromonomers MM(1) 104(1) to distinguish them from the aforementioned difunctional macromonomers that form multibranched polymerizations, such as... Figure 5C As shown. Figure 12 As shown, when the activated photoinitiator PI* activates such a monofunctional mobile macromonomer MM(1) 104(1), chain polymerization can subsequently begin, but the clusters of chain polymerization will have a linear backbone or zigzag ridges, but no secondary and additional branches. Therefore, chain polymerization will be suppressed and limited after UV irradiation stops, thereby reducing the probability and extent of non-targeted power drift. It is worth mentioning that LAL 100 with such a monofunctional mobile macromonomer MM(1) 104(1), although they have less or even negligible non-targeted power drift, may also limit regulated UV irradiation to induce less (targeted) power change. The power change achievable by UV irradiation can be about 2.0-2.5 D in LAL with bifunctional MM 104, while it is only 0.4-0.7 D in LAL with monofunctional MM(1) 104(1).

[0171] (5) Other embodiments of LAL 100 still employ a polymerization-controlled design and suppress undesirable power drift by introducing a sterically hindered, mobile macromonomer MM(sh) 104(sh). The chemically activatable bond in the generic acrylate end group Xa 103a of MM 104(sh) is a double bond between the last and penultimate carbon atoms:

[0172]

[0173] The sterically hindered end group 103(sh) contains additional ligands surrounding the C=C double bond to sterically impede access to the radical center of the photoactivated photoinitiator PI*106*. For example, in the methacrylate end group 103, the H on the penultimate C is replaced by CH3. Other sterically hindered MM 104(sh) replaces the two hydrogens at the last C with other carbon atoms, each of which may form a CH3 or longer chain. Still other sterically hindered MM 104(sh) replaces the three hydrogens of the CH3 group at the penultimate C of the methacrylate end group 103 with carbon atoms, each of which may form a CH3 or longer chain. In other sterically hindered MM 104(sh), the carbon atom of the activated double bond of the end group 103(sh) of the mobile macromonomer MM 104(sh) also forms a bond with a CH3 methyl group or a longer chain. In other sterically hindered MM 104(sh), the carbon atom of the activated double bond of the terminal group 103(sh) of the mobile macromonomer MM 104(sh) also forms a bond with such a carbon atom, which is coupled with at least one other carbon atom. In still other sterically hindered MM 104(sh), the last or penultimate carbon atom of the activated double bond of the acrylate terminal group 103(sh) of the mobile macromonomer MM 104(sh) also forms a bond with a CH3 methyl group or a longer chain.

[0174] Other methods extend the chain attached to end group 103, for example by using propyl acrylate, isopropyl acrylate, tert-butyl acrylate, sec-butyl acrylate, butyl acrylate, cyclohexyl acrylate, cyclopentyl acrylate, and phenyl acrylate. Each of these sterically hindered structures tends to reduce the rate of subsequent chain polymerization, thereby reducing the rate of undesirable power drift.

[0175]

[0176] (6) In some LAL 100 embodiments, power drift can be reduced by redesigning the underlying Si polymer network 101. Recall that the mobile macromonomer MM preferentially bonds to the polymer network 101 at its vertices, which is generated by the crosslinking agent XLK 102. Therefore, the polymer silicone network 101 with less crosslinking agent XLK 102 provides fewer connection vertices, where the mobile macromonomer MM can bond to the underlying silicone network. Forming the silicone network 101 with less crosslinking agent 102 suppresses one of the two main processes of immobilized macromonomers, such as Figure 5A As shown. Therefore, LAL 100 with such a reduced crosslinker density exhibits reduced power drift. It is worth mentioning that less crosslinker tends to make LAL 100 softer. In addition, other polymer control designs reduce the introduction of MM 104 into the Si network 101 during LAL 100 curing.

[0177] (7) In other embodiments, the power drift is reduced through different designs of the pre-protective layer 110. The pre-protective layer 110 has been described as containing a switchable UV absorber or UV blocker. However, as previously mentioned, some switchable UV blockers degrade over time, induced by free radicals in the system such as PI*106* or XOO* radicals. The degradation of the switchable UV absorber over time results in an increase in the fraction of incident UV photons passing through the pre-protective layer 110, which acts as another driving factor for non-targeted power drift.

[0178] To reduce this increase in UV penetration through the front protective layer 110, in some embodiments the front protective layer 110 may be formed from a combination of switchable and non-switchable UV blocking agents. In such a LAL 100, any potential degradation of the switchable UV blocking agent results only in a partial loss of UV blocking, because the permanent UV blocking agent does not degrade and does not lose its ability to block UV light over time. In some LAL 100s, the non-switchable UV absorber constitutes 5-50% of the combined amount of the switchable and non-switchable UV absorbers in the front protective layer 110. In some other embodiments, this fraction is 10-40%, and in still other embodiments it is 20-30%.

[0179] Several additional issues may arise when selecting non-switchable UV absorbers. One of these is that some switchable UV absorbers (such as VPAP) result in a more yellow visual experience than is comfortable for the patient, because the absorption spectrum of VPAP has a tail that extends into the visible spectrum above 400 nm. Figure 13As shown. Therefore, the added non-switchable UV blocker can preferably be selected based on its property that it provides strong UV blocking for wavelengths less than 400 nm, but minimal blocking for wavelengths greater than 400 nm, such as Figure 13 As shown. In other words, in some LAL 100s, the non-switchable UV absorber effectively absorbs wavelengths shorter than 400 nm. Since these wavelengths do not affect the control of the polymerization process and do not help suppress unwanted power drift, they are not a component or necessary part of the polymerization control design. Instead, they are designed to improve the overall visual experience of the patient. Examples include UV absorbers that effectively absorb at wavelengths shorter than 380 nm or 390 nm. A wide variety of suitable non-switchable UV absorbers or UV blockers have been described in US 6851804, entitled “Readjustable optical elements” by JM Jethmalani et al., and US 9119710, entitled “Adjustable optical elements with enhanced ultraviolet protection” by RH Grubbs et al., both of which are incorporated herein by reference in their entirety.

[0180] (8) As described above, in LAL 100, the switchable UV absorber in the preprotective layer 110 can undergo partial degradation over time due to reaction with free radicals, primarily PI*106* or XOO* free radicals diffused from the LAL 100 bulk into the preprotective layer 110, or free radicals generated by UV radiation after unactivated PI 106a has diffused into the preprotective layer 110. To suppress this degradation mechanism, some LAL 100s inhibit the diffusion of PI 106 into the preprotective layer 110. The hydrophobic PI 106 photoinitiator diffuses efficiently into the hydrophobic silicon matrix 101 of the bulk and the preprotective layer 110. The water content of the hydrophobic bulk and the preprotective layer is typically 4% or less. In contrast, some LAL 100s employ a polymerization-controlled design by adding water to their preprotective layers 110, thereby preventing the diffusion of hydrophobic PI 106 into their preprotective layers 110. Some LAL 100s have a water content of 4%–20% in their pre-protective layer, while others have 5%–10%. Other control designs alter the hydrophobicity of the silicone polymer network 101, while others alter the hydrophobicity of the mobile macromonomer 104 to change the hydrophobicity of the pre-protective layer 110, thereby suppressing the internal diffusion of PI. Each of these polymer control designs reduces the degradation of the switchable UV absorber and thus ultimately reduces undesirable power drift of the LAL 100. Some control designs may introduce an additional insulating layer between the LAL 100 body and the pre-protective layer 110 to suppress the internal migration of free radicals PI* 106* and XOO*.

[0181] (9) In some LAL 100 embodiments, the photoinitiator PI itself can be switched between a protected state and an activated state. In some sense, the protected state can be referred to as a “cage-bound” state. In some embodiments, UV-sensitive bonds that can be activated by incoming UV photons are protected by their molecular environment. For such a switchable PI to function, the protected state must first be switched or altered so that subsequent UV photons can disrupt the UV-sensitive bonds themselves. The protected state can be switched by a first wavelength of light that differs from a second wavelength of UV light used in the forming irradiation, which activates the photoinitiator PI 106 to modulate and lock the LAL 100. For example, a shorter wavelength of UV light can be used to alter such a protected state, which is designed to absorb only such shorter wavelength radiation. Since these switchable PI 106s are “on demand,” they are deactivated in the absence of activating UV light and therefore do not induce any unwanted polymerization and power drift. In other words, the photoinitiator PI 106 is less photoactivated in the protected state than in the activated state. In some embodiments, the photoinitiator is minimally photoactivated in the protected state.

[0182] Such switchable PIs do not necessarily rely on traditional multiphoton processes. Multiphoton processes are typically inefficient and therefore require high beam intensities exceeding retinal safety levels. In these processes, a first photon typically excites an electron to a first intermediate state, and then a second photon excites the same electron to a higher-energy target state. In this case, the excitation of this second electron constitutes the activation of PI 106. Since the first intermediate state has a very short lifetime in many multiphoton processes, the second photon must be incident very shortly after the first photon, typically within picoseconds or nanoseconds. These short electron lifetimes require high intensity. In contrast, in implementations of switchable PIs, the protective structure is a protective bond or conformation that can have a long lifetime in its switched state after absorbing the first photon. Therefore, the second photon can arrive relatively late and still activate the UV-sensitive bonds of PI 106. Thus, lower-intensity beams can successfully operate these switchable PI control designs.

[0183] (10) In other embodiments, the photoinitiator PI 106 itself may be anchored to network 101. In such a system, the anchored PI 106 can still activate the mobile macromonomer MM 104. However, physically, these anchored PI 106 are mechanically and dynamically prevented from reaching the activatable end groups 103 of the mobile macromonomer MM 104 and the fixed macromonomer IM 105. Specifically, the shaping irradiation activates the photoinitiator PI 106 by breaking it down into two radicals PI*106*, wherein at least one of the radicals remains attached to the polymeric silicone network 101. Therefore, the anchored PI 106 is less effective at inducing the chain polymerization process and is therefore less likely to induce undesirable power drift. Some LAL 100s with such anchored PI 106 may exhibit history dependence, which needs to be addressed. In some control designs, irradiation modes corresponding to different irradiation histories can be developed.

[0184] (11) In other LAL 100 embodiments, power drift is prevented by completely omitting the photoinitiator PI 106. In such a LAL 100, polymerization of the mobile macromonomer MM 104 is directly induced by a two-photon or multi-photon process. Initiating such a process typically requires higher intensity irradiation. Therefore, in such a LAL 100, UV irradiation can be delivered by a laser, possibly in a scanning operation with close focusing. If two photons of 500 nm wavelength from such a laser sequentially strike the mobile macromonomer MM 104 fast enough, they can directly induce polymerization chemistry of the type of processes (1) and (2) in MM 104: this process would otherwise be induced by a single UV photon of 250 nm wavelength to correct for losses. In contrast to the above process, no equivalent of PI* radical 106* is generated in such a LAL, and therefore there is no corresponding induced power drift after irradiation stops.

[0185] While this document contains numerous provisions, details, and numerical ranges, these should not be construed as limiting the scope of the invention and the claims, but rather as descriptions of specific features of particular embodiments of the invention. Some features described in the context of individual embodiments may also be implemented in combination in a single embodiment. Conversely, different features described in the context of a single embodiment may also be implemented individually or in any suitable sub-combination in multiple embodiments. Furthermore, although features may be described above as functioning in some combination and even initially claimed in this way, one or more features from a claimed combination may be removed from said combination in some cases, and the claimed combination may involve another sub-combination or a variation of a sub-combination.

Claims

1. Light-adjustable lens (LAL) comprising: a polymeric silicone network infused with a mobile macromer, a non-switchable ultraviolet absorber, and a photoinitiator; and a front protective layer comprising a switchable ultraviolet absorber; wherein the LAL is light-adjustable by a shaping irradiation that activates the photoinitiator, which induces polymerization of the mobile macromer, thereby changing the optical power of the LAL; the LAL is capable of accommodating oxygen concentrations in the range of 0.5-20 ppm; and the LAL comprises a radical scavenger or antioxidant.

2. Light-adjustable lens according to claim 1, wherein the concentration of the radical scavenger is in the range of 5-1000 ppm.

3. Light-adjustable lens according to claim 1, wherein: the concentration of the radical scavenger is in the range of 10-500 ppm.

4. Light-adjustable lens according to claim 1, wherein: the concentration of the radical scavenger is in the range of 50-200 ppm.

5. Light-adjustable lens according to claim 1, wherein: the radical scavenger is tocopherol, or vitamin E.

6. Light-adjustable lens according to claim 1, wherein: the photoinitiator is capable of becoming an activated photoinitiator upon absorption of a UV photon; and the activated photoinitiator is capable of activating the mobile macromer by activating an end group of the mobile macromer.

7. Light-adjustable lens according to claim 6, wherein: the activated end group of the mobile macromer is capable of forming a bond with a second mobile macromer, activating an end group of the second mobile macromer in the process.

8. Light-adjustable lens according to claim 6, wherein: the reaction of the activated photoinitiator with oxygen produces a low-activity photoinitiator derivative.

9. Light-adjustable lens according to claim 6, wherein: the reaction of the activated mobile macromer with oxygen produces a low-activity compound; and the LAL comprises a radical scavenger capable of reacting with the low-activity compound to convert it into an inactivated compound.

10. Light-adjustable lens according to claim 1, wherein: the switchable UV absorber is selected from azobenzene, azo-aromatics, diazene, azo- pyrazole, dienyl ethylene, fulgimide, azulene, spiropyran, ethylene-aromatics, a macromer of one of these compounds, a polymer of one of these compounds, a composition containing one of these compounds, a composition containing one of these compounds as a side chain, a composition containing one of these compounds as a backbone with side chains, a nanoparticle bonded to one of these compounds, 4-methoxyazobenzene, indazoles, allylized azobenzenes with different spacer linkages, phenylazo pyrazoles, vinyl phenyl azo-pyrazoles, and stilbenes.

11. Light-adjustable lens according to claim 1, wherein: the front protective layer comprises a non-switchable ultraviolet absorber.

12. Light-adjustable lens according to claim 1, comprising: a radical scavenger or antioxidant.

13. The light-tunable lens of claim 1, wherein: the mobile macromers are monofunctional.

14. The light-tunable lens of claim 1, wherein: the mobile macromers are sterically hindered.

15. The light-tunable lens of claim 1, wherein: the photoinitiator is switchable between a protected state and an activatable state.

16. The light-tunable lens of claim 1, wherein: the chemical composition, concentration, and reaction rates of the silicone network, the mobile macromers, the switchable and non-switchable UV absorbers, and the photoinitiator are such that the slope of the time-dependent power adjustment curve increases by a factor of two or more after a t(activation) time, where t(activation) is in the range of 3 seconds to 100 seconds, during the light adjustment procedure.

17. The light-tunable lens of claim 1, wherein: the photoinitiator is anchored to the polymeric silicone network.

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