Abstract:
High refractive index copolymers suitable for use in ophthalmic devices are disclosed. The copolymers comprise two or more aryl hydrophobic monomers and a non-polymerizable propylene oxide-ethylene oxide-propylene oxide block copolymer surfactant having a molecular weight of approximately 3600 and approximately 40% ethylene oxide units by weight. The copolymers have a reduced tendency to form glistenings when stored in water at physiological temperatures compared to similar copolymers lacking the non-polymerizable surfactant.

Description:
This application claims priority to U.S. Provisional Application, U.S. Ser. No. 60/951,865 filed Jul. 25, 2007. 
    
    
     FIELD OF THE INVENTION 
     This invention relates to high refractive index polymers and their use in ophthalmic lenses, particularly intraocular lenses that can be inserted through small incisions. 
     BACKGROUND OF THE INVENTION 
     High refractive index acrylic materials are known for use in intraocular lenses (IOLs). For example, U.S. Pat. No. 5,290,892 discloses high refractive index acrylic materials suitable for use as IOL materials. The materials are foldable and thus capable of being inserted through small incisions. These acrylic materials contain, as principal components, two aryl acrylic monomers. 
     In some cases, foldable acrylic intraocular lenses develop “glistenings” or “vacuoles” when implanted in humans or soaked in water at physiological temperatures. These microvacuoles appear to be pockets of water approximately 1 μm or greater in diameter. Glistenings are often too small to be seen by the naked eye, but are sometimes observed using a slit-lamp. Although glistenings have no detrimental effect on the function or performance of IOLs made from acrylic materials, it is nevertheless cosmetically desirable to minimize or eliminate them. 
     Published U.S. Patent Application 2006/0275342 A1 discloses ophthalmic device materials, including IOL materials, containing less than 15% by weight of certain polymerizable surfactants. The polymerizable surfactants are poloxamers and poloxamines, which are generally available under the PLURONIC and TETRONIC tradenames. One advantage of adding such polymerizable surfactants as comonomers in forming polymeric devices is said to be changed or improved device surface properties, such as lipid or protein uptake. It was determined that the functionalized surfactants did not affect mechanical properties of the device materials as the addition of the polymerizable surfactants produced no real change in the modulus or tear strength (see Example 17 of 2006/0275342 A1). The surfactants are chemically modified to make them polymerizable as comonomers. When unmodified surfactants were incorporated into a hydrogel contact lens material during polymerization, it was noted that upon hydration the lenses would become cloudy. When methacrylated counterparts of the unmodified surfactants were used, however, optical clarity was maintained after hydration (see Example 16 and FIGS. 6-8 of 2006/0275342 A1). 
     SUMMARY OF THE INVENTION 
     This invention is directed to ophthalmic device materials that do not contain glistenings. The ophthalmic device materials comprise
     a) two polymerizable monomers of the structure:   

                                
wherein:
         X is H or CH 3 ;   m is 0-6;   Y is nothing, O, or O(CH 2 CH 2 O) n ;   n is 1-6;   w is 0-6, provided that m+w≦8; and   Ar is phenyl which can be unsubstituted or substituted with CH 3 , C 2 H 5 , n-C 3 H 7 , iso-C 3 H 7 , OCH 3 , C 6 H 11 , Cl, Br, C 6 H 5 , or CH 2 C 6 H 5 ;       b) a polymerizable cross-linking agent; and   c) a non-polymerizable propylene oxide-ethylene oxide-propylene oxide block copolymer surfactant having a molecular weight of approximately 3600 and an ethylene oxide unit content of approximately 40% by weight.   
     These device materials can be used to form intraocular lenses that have high refractive indexes, are flexible and transparent, can be inserted into the eye through a relatively small incision, and recover their original shape after having been inserted. Moreover, IOLs made from these materials are free or substantially free of glistenings compared to otherwise identical materials lacking the non-polymerizable surfactant. 
     Among other factors, the present invention is based upon the finding that the ophthalmic device materials obtained by copolymerizing two monomers of structure (I) and a cross-linking agent with a non-polymerizable propylene oxide-ethylene oxide-propylene oxide block copolymer surfactant having a molecular weight of approximately 3600 and an ethylene oxide unit content of approximately 40% are clear. Additionally, unlike when other propylene oxide-ethylene oxide-propylene oxide block copolymer surfactants are added to two monomers of structure (I) to obtain ophthalmic device materials, when a non-polymerizable propylene oxide-ethylene oxide-propylene oxide block copolymer surfactant having a molecular weight of approximately 3600 and an ethylene oxide unit content of approximately 40% by weight is added, the device materials are free or substantially free of glistenings. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The ophthalmic device materials of the present invention comprise two monomers of the structure: 
                                
wherein:
         X is H or CH 3 ;   m is 0-6;   Y is nothing, O, or O(CH 2 CH 2 O) n ;   n is 1-6;   w is 0-6, provided that m+w≦8; and   Ar is phenyl which can be unsubstituted or substituted with CH 3 , C 2 H 5 , n-C 3 H 7 , iso-C 3 H 7 , OCH 3 , C 6 H 11 , Cl, Br, C 6 H 5 , or CH 2 C 6 H 5 .       
     Monomers of structure (I) can be made by methods known in the art. For example, the conjugate alcohol of the desired monomer can be combined in a reaction vessel with methyl methacrylate, tetrabutyl titanate (catalyst), and a polymerization inhibitor such as 4-benzyloxy phenol. The vessel can then be heated to facilitate the reaction and distill off the reaction by-products to drive the reaction to completion. Alternative synthesis schemes involve adding methacrylic acid to the conjugate alcohol and catalyzing with a carbodiimide or mixing the conjugate alcohol with methacryloyl chloride and a base such as pyridine or triethylamine. 
     Suitable monomers of structure (I) include, but are not limited to: 2-ethylphenoxy methacrylate; 2-ethylphenoxy acrylate; phenyl methacrylate; phenyl acrylate; benzyl methacrylate; benzyl acrylate; 2-phenylethyl methacrylate; 2-phenylethyl acrylate; 3-phenylpropyl methacrylate; 3-phenylpropyl acrylate; 4-phenylbutyl methacrylate; 4-phenylbutyl acrylate; 4-methylphenyl methacrylate; 4-methylphenyl acrylate; 4-methylbenzyl methacrylate; 4-methylbenzyl acrylate; 2-2-methylphenylethyl methacrylate; 2-2-methylphenylethyl acrylate; 2-3-methylphenylethyl methacrylate; 2-3-methylphenylethyl acrylate; 2-4-methylphenylethyl methacrylate; 2-4-methylphenylethyl acrylate; 2-(4-propylphenyl)ethyl methacrylate; 2-(4-propylphenyl)ethyl acrylate; 2-(4-(1-methylethyl)phenyl)ethyl methacrylate; 2-(4-(1-methylethyl)phenyl)ethyl acrylate; 2-(4-methoxyphenyl)ethyl methacrylate; 2-(4-methoxyphenyl)ethyl acrylate; 2-(4-cyclohexylphenyl)ethyl methacrylate; 2-(4-cyclohexylphenyl)ethyl acrylate; 2-(2-chlorophenyl)ethyl methacrylate; 2-(2-chlorophenyl)ethyl acrylate; 2-(3-chlorophenyl)ethyl methacrylate; 2-(3-chlorophenyl)ethyl acrylate; 2-(4-chlorophenyl)ethyl methacrylate; 2-(4-chlorophenyl)ethyl acrylate; 2-(4-bromophenyl)ethyl methacrylate; 2-(4-bromophenyl)ethyl acrylate; 2-(3-phenylphenyl)ethyl methacrylate; 2-(3-phenylphenyl)ethyl acrylate; 2-(4-phenylphenyl)ethyl methacrylate; 2-(4-phenylphenyl)ethyl acrylate; 2-(4-benzylphenyl)ethyl methacrylate; and 2-(4-benzylphenyl)ethyl acrylate. 
     Preferred monomers of structure (I) are those wherein m is 2-4, Y is nothing or O, and Ar is phenyl. Most preferred are 2-phenylethyl acrylate and 2-phenylethyl methacrylate. 
     The total amount of the monomers of structure (I) contained in the device materials of the present invention is generally about 75% by weight or more, and is preferably about 80-90% by weight, of the total amount of polymerizable components of the ophthalmic device materials. 
     The ophthalmic device materials of the present invention also contain a polymerizable cross-linking agent. The cross-linking agent may be any terminally ethylenically unsaturated compound having more than one unsaturated group. Suitable cross-linking agents include, for example: ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, allyl methacrylate, 1,3-propanediol dimethacrylate, 1,6-hexanediol dimethacrylate, 1,4-butanediol dimethacrylate, and their corresponding acrylates. Preferred cross-linking agents are ethylene glycol dimethacrylate (EGDMA) and 1,4-butanediol diacrylate (BDDA). In general, the amount of any cross-linking agent used in the device materials of the present invention will be 10% by weight or less, preferably 5% by weight or less, of the polymerizable components of the ophthalmic device materials. In preferred embodiments, the device materials of the present invention comprise a cross-linking agent in an amount of 0.2-5% by weight. In even more preferred embodiments, the device materials of the present invention comprise a cross-linking agent in an amount of 2-5% by weight. 
     In addition to two monomers of structure (I), the copolymers of the present invention also contain a non-polymerizable propylene oxide-ethylene oxide-propylene oxide block copolymer surfactant having a molecular weight of approximately 3600 and an ethylene oxide unit content of approximately 40% by weight. Such a surfactant is commercially available from BASF under the tradename Pluronic® 25R4. The amount of Pluronic 25R4 contained in the ophthalmic device materials of the present invention is generally 2-20% by weight, and is preferably 4.5-10.5% by weight. 
     The proportions of the monomers to be included in the copolymers of the present invention should be chosen so that the copolymer has a glass transition temperature (T g ) not greater than about 37° C., which is normal human body temperature. Copolymers having glass transition temperatures higher than 37° C. are not suitable for use in foldable IOLs; such lenses could only be rolled or folded at temperatures above 37° C. and would not unroll or unfold at normal body temperature. It is preferred to use copolymers having a glass transition temperature somewhat below normal body temperature and no greater than normal room temperature, e.g., about 20-25° C., in order that IOLs made of such copolymers can be rolled or folded conveniently at room temperature. T g  is measured by differential scanning calorimetry at 10° C./min., and is determined at the midpoint of the transition of the heat flux curve. 
     For IOLs and other applications, the materials of the present invention must exhibit sufficient strength to allow devices made of them to be folded or manipulated without fracturing. Thus the copolymers of the present invention will have an elongation of at least 80%, preferably at least 100%, and most preferably between 110 and 200%. This property indicates that lenses made of such materials generally will not crack, tear or split when folded. Elongation of polymer samples is determined on dumbbell shaped tension test specimens with a 20 mm total length, length in the grip area of 4.88 mm, overall width of 2.49 mm, 0.833 mm width of the narrow section, a fillet radius of 8.83 mm, and a thickness of 0.9 mm. Testing is performed on samples at ambient conditions using an Instron Material Tester (Model No. 4442 or equivalent) with a 50 Newton load cell. The grip distance is set at 14 mm and a crosshead speed is set at 500 mm/minute and the sample is pulled until failure. The elongation (strain) is reported as a fraction of the displacement at failure to the original grip distance. Since the materials to be tested are essentially soft elastomers, loading them into the Instron machine tends to make them buckle. To remove the slack in the material sample a pre-load is placed upon the sample. This helps to reduce the slack and provide a more consistent reading. Once the sample is pre-loaded to a desired value (typically 0.03 to 0.05 N) the strain is set to zero and the test begun. 
     IOLs made of the ophthalmic device materials of the present invention are free or substantially free of glistenings when measured according to the following test (“the Glistening Test”). The presence of glistenings is measured by placement of a lens or disk sample into a vial and adding deionized water or a balanced salt solution. The vial is then placed into a water bath preheated to 45° C. Samples are to be maintained in the bath for 24±2 hours. The vial is then removed from the water bath and allowed to equilibrate at room temperature for 2±0.5 hours. The sample is removed from the vial and placed on a microscope slide. The sample is inspected visually in various on angle or off angle lighting to evaluate clarity. Visualization of glistenings is done with light microscopy using a magnification of 50 to 200×. A sample is judged to be free of glistenings if, at 50-200× magnification, the number of glistenings detected in the eyepiece is zero. A sample is judged to be substantially free of glistenings if, at 50-200× magnification, the number of glistenings detected in the eyepiece is less than about 2/mm 3 . It is often very difficult to detect glistenings, so the sample is rastered throughout the entire volume of the lens, varying the magnification levels (50-200×), the aperture iris diaphragm, and the field conditions (using both bright field and dark field conditions) in an attempt to detect the presence of glistenings. 
     An ultra-violet absorbing material can also be included in the materials of the present invention. The ultraviolet absorbing material can be any compound which absorbs ultraviolet light, i.e., light having a wavelength shorter than about 400 nm, but does not absorb any substantial amount of visible light. The ultraviolet absorbing compound is incorporated into the monomer mixture and is entrapped in the polymer matrix when the monomer mixture is polymerized. Suitable ultraviolet absorbing compounds include substituted benzophenones, such as 2-hydroxybenzophenone, and 2-(2-hydroxyphenyl)benzotriazoles. It is preferred to use an ultraviolet absorbing compound which is copolymerizable with the monomers and is thereby covalently bound to the polymer matrix. In this way possible leaching of the ultraviolet absorbing compound out of the lens and into the interior of the eye is minimized. Suitable copolymerizable ultraviolet absorbing compounds are the substituted 2-hydroxybenzophenones disclosed in U.S. Pat. No. 4,304,895 and the 2-hydroxy-5-acryloxyphenyl-2H-benzotriazoles disclosed in U.S. Pat. No. 4,528,311. The most preferred ultraviolet absorbing compound is 2-(2′-hydroxy-3′-methallyl-5′-methyl phenyl) benzotriazole. 
     In addition to ultraviolet absorbing materials, ophthalmic devices made of the copolymers of the present invention may include colored dyes, such as the yellow dyes disclosed in U.S. Pat. No. 5,470,932. 
     The copolymers of this invention are prepared by conventional polymerization methods. For example, a mixture of the liquid monomers of structure (I) and a cross-linking agent in the desired proportions, together with the non-polymerizable surfactant, a UV absorber, a yellow dye, and a conventional thermal free-radical initiator, is prepared. The mixture can then be introduced into a mold of desired shape, and the polymerization carried out by heating to activate the initiator. Typical thermal free radical initiators include peroxides, such as benzoyl peroxide, peroxycarbonates, such as bis-(4-t-butylcyclohexyl) peroxydicarbonate, azonitriles, such as azobisisobutyronitrile, and the like. A preferred initiator is bis-(4-t-butylcyclohexyl) peroxydicarbonate (PERK). Alternatively, the monomers can be photopolymerized by using a mold which is transparent to actinic radiation of a wavelength capable of initiating polymerization of these acrylic monomers by itself. Conventional photoinitiator compounds, e.g., a benzophenone-type photoinitiator, can also be introduced to facilitate the polymerization. 
     Once the ophthalmic device materials of the present invention have been cured, they are extracted in a suitable solvent to remove as much of the unreacted components of the materials as possible. Examples of suitable solvents include acetone, methanol, and cyclohexane. A preferred solvent for extraction is acetone. 
     IOLs constructed of the disclosed ophthalmic device materials can be of any design capable of being rolled or folded into a small cross section that can fit through a relatively smaller incision. For example, the IOLs can be of what is known as a one piece or multipiece design. Typically, an IOL comprises an optic and at least one haptic. The optic is that portion which serves as the lens and the haptics are attached to the optic and are like arms which hold the optic in its proper place in the eye. The optic and haptic(s) can be of the same or different material. A multipiece lens is so called because the optic and the haptic(s) are made separately and then the haptics are attached to the optic. In a single piece lens, the optic and the haptics are formed out of one piece of material. Depending on the material, the haptics are then cut, or lathed, out of the material to produce the IOL. 
     In addition to IOLs, the ophthalmic device materials of the present invention are also suitable for use in other devices, including contact lenses, keratoprostheses, intracorneal lenses, corneal inlays or rings, and glaucoma filtration devices. 
     The invention will be further illustrated by the following examples which are intended to be illustrative, but not limiting. 
     Example 1 
     A stock lens solution containing 65% 2-phenylethyl acrylate, 30% 2-phenylethyl methacrylate, 3.2% 1,4-butanediol diacrylate, 1.8% o-methallyl Tinuvin P, and 1.8% Perkadox 16 was prepared. The lens formulations shown below in Table 1 were prepared by combining the indicated amounts of the stock lens solution with the indicated amounts of non-polymerizable Pluronic 25R4. The resulting formulation was added to slab molds and cured in a forced air oven at 70-80° C. for 1 hr then ramp to 100-110° C. and held there for 2 hours and after curing, the slabs were extracted (bulk) in the indicated solvents, tested for glistening (vacuoles) using the test described above, inspected to determine whether they were clean or hazy, and analyzed to determine equilibrium water content at 35° C. The results are shown in Table 1. 
     
       
         
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                 Stock 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Lens 
                 Pluronic 
                   
                   
                   
                   
                 35° C. 
               
               
                 Formulation 
                 Solution 
                 25R4 
                 Solvent 
                 Extracts 
                   
                   
                 EWC 
               
               
                 No. 
                 (%) 
                 (%) 
                 Extraction 
                 (%) 
                 Vacuoles 
                 Clarity 
                 (%) 
               
               
                   
               
             
             
               
                 1 
                 90 
                 10 
                 None 
                 — 
                 None 
                 Clear 
                 — 
               
               
                 2 
                 90 
                 10 
                 Methanol 
                 2.80 
                 None 
                 Clear 
                 2.80 
               
               
                 3 
                 90 
                 10 
                 Cyclohexane 
                 3.03 
                 None 
                 Clear 
                 2.37 
               
               
                 4 
                 90 
                 10 
                 Acetone 
                 9.24 
                 None 
                 Clear 
                 0.71 
               
               
                   
               
             
          
         
       
     
     Example 2 
     The lens formulations shown in Table 2 were prepared and cured according to the procedure described in Example 1. All cured slabs were subjected to soxhlet acetone extraction with a desired number of cycles. In addition to the tests conducted in Example 1, refractive index was also measured. The results are shown in Table 2 
     
       
         
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                   
                 Stock 
                   
                 # Soxhlet 
                   
                   
                   
                 35° C. 
                   
               
               
                 Formulation 
                 Lens 
                 Pluronic 
                 Extraction 
                   
                   
                   
                 EWC 
                 Refractive 
               
               
                 No. 
                 Solution 
                 25R4 
                 Cycles 
                 Extracts % 
                 Vacuoles 
                 Clarity 
                 (%) 
                 Index 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 5 
                 90.01 
                 9.99 
                 5 
                 5.37 
                 None 
                 Clear 
                 1.91 
                 1.526 
               
               
                 6 
                 90.01 
                 9.99 
                 10 
                 7.52 
                 None 
                 Clear 
                 1.34 
                 1.534 
               
               
                 7 
                 90.01 
                 9.99 
                 15 
                 8.18 
                 None 
                 Clear 
                 1.08 
                 1.537 
               
               
                 8 
                 90.01 
                 9.99 
                 20 
                 8.52 
                 None 
                 Clear 
                 0.97 
                 1.538 
               
               
                 9 
                 90.01 
                 9.99 
                 25 
                 8.75 
                 None 
                 Clear 
                 0.93 
                 1.538 
               
               
                   
               
             
          
         
       
     
     Example 3 
     The lens formulations shown in Table 3 were prepared and cured in a manner similar to Example 1. The formulations were subjected to either a one-state or two-stage acetone extraction process where the first stage was soxhlet extraction and the second stage was simple (static) extraction. Vacuole testing and clarity inspections were conducted as shown and equilibrium water content was determined. The results are shown in Table 3. For Examples 3-9, the quantity of vacuoles present in a sample was not determined by any measurements or counting, but a rough estimate of the number of vacuoles observed was noted using the following hierarchy: full&gt;some&gt;few&gt;none. 
     
       
         
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
               
                   
               
               
                   
                 Stock 
                   
                   
                   
                 Vacuoles 
                 Clarity 
                 Vacuoles 
                 Clarity 
                   
               
               
                 Formulation 
                 Lens 
                 Pluornic 
                 Extraction 
                 Extracts 
                 Pre- 
                 Pre- 
                 Post- 
                 Post 
                 35° C. 
               
               
                 No. 
                 Solution 
                 25R4 
                 Condition 
                 (%) 
                 Extraction 
                 Extraction 
                 Extraction 
                 Extraction 
                 EWC % 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 10 
                 100 
                 0 
                 Soxh. 
                 2.09 
                 Yes (full) 
                 Clear 
                 Yes (full) 
                 Very 
                 0.32 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 slight 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 haze 
               
               
                 11 
                 100 
                 0 
                 Soxh./static 
                 2.21 
                 — 
                 — 
                 Yes (full) 
                 Slight 
                 0.32 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 haze 
               
               
                 12 
                 97.23 
                 2.77 
                 Soxh. 
                 3.64 
                 None 
                 Clear 
                 * 
                 Clear 
                 0.43 
               
               
                 13 
                 97.23 
                 2.77 
                 Soxh./static 
                 3.88 
                 — 
                 — 
                 Yes, but 
                 Clear 
                 0.39 
               
               
                   
                   
                   
                   
                   
                   
                   
                 less than 
               
               
                   
                   
                   
                   
                   
                   
                   
                 control 
               
               
                 14 
                 95.03 
                 4.97 
                 Soxh. 
                 5.04 
                 None 
                 Clear 
                 * 
                 Clear 
                 0.55 
               
               
                 15 
                 95.03 
                 4.97 
                 Soxh./static 
                 5.46 
                 — 
                 — 
                 None 
                 Clear 
                 0.44 
               
               
                 16 
                 92.34 
                 7.66 
                 Soxh. 
                 7.10 
                 None 
                 Clear 
                 * 
                 Clear 
                 0.67 
               
               
                 17 
                 92.34 
                 7.66 
                 Soxh./static 
                 7.39 
                 — 
                 — 
                 None 
                 Clear 
                 0.60 
               
               
                 18 
                 89.86 
                 10.14 
                 Soxh. 
                 9.07 
                 None 
                 Clear 
                 None 
                 Clear 
                 0.79 
               
               
                 19 
                 89.86 
                 10.14 
                 Soxh./static 
                 9.32 
                 — 
                 — 
                 None 
                 Clear 
                 0.81 
               
               
                   
               
               
                 * Very few spots; not immediately recognized as vacuoles. 
               
             
          
         
       
     
     Example 4 
     The lens formulations shown in Table 4 were prepared and cured in a manner similar to Example 1. The cured slabs were bulk extracted in acetone followed by methylene chloride as indicated. The samples were tested for vacuoles, inspected for clarity and equilibrium water content at 35° C. was determined. The results are shown in Table 4. 
     
       
         
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
               
                   
               
               
                   
                 Stock 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Lens 
                 Pluronic 
               
               
                 Formulation 
                 Solution 
                 25R4 
                 Solvent 
                 Extracts 
                   
                   
                 35° C. 
               
               
                 No. 
                 (%) 
                 (%) 
                 Extraction 
                 (%) 
                 Vaculoes 
                 Clarity 
                 EWC (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 20 
                 100 
                 0 
                 Acetone 
                 2.16 
                 Yes (full) 
                 Slight 
                 0.38 
               
               
                   
                   
                   
                   
                   
                   
                 haze 
               
               
                 21 
                 94.93 
                 5.07 
                 Acetone 
                 5.37 
                 None 
                 Clear 
                 0.50 
               
               
                 22 
                 92.24 
                 7.76 
                 Acetone 
                 7.37 
                 None 
                 Clear 
                 0.56 
               
               
                 23 
                 89.90 
                 10.10 
                 Acetone 
                 9.24 
                 None 
                 Clear 
                 0.79 
               
               
                 24 
                 100 
                 0 
                 CH 2 Cl 2   
                 2.24 
                 Yes (full) 
                 Slight 
                 0.35 
               
               
                   
                   
                   
                   
                   
                   
                 haze 
               
               
                 25 
                 94.93 
                 5.07 
                 CH 2 Cl 2   
                 6.09 
                 None 
                 Clear 
                 0.51 
               
               
                 26 
                 92.24 
                 7.76 
                 CH 2 Cl 2   
                 7.64 
                 None 
                 Clear 
                 0.62 
               
               
                 27 
                 89.90 
                 10.10 
                 CH 2 Cl 2   
                 9.51 
                 None 
                 Clear 
                 0.72 
               
               
                   
               
             
          
         
       
     
     Example 5 
     The lens formulations shown in Table 5 were prepared and cured in a manner similar to Example 1. The slabs were bulk extracted in acetone, tested for vacuoles and equilibrium water content at 35° C. was determined. The results are shown in Table 5. 
     
       
         
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
               
                   
               
               
                 Formulation 
                 Stock Lens 
                 Pluronic 
                 Extracts 
                   
                 35° C. 
               
               
                 No. 
                 Solution (%) 
                 25R4 
                 % 
                 Vacuoles 
                 EWC (%) 
               
               
                   
               
             
             
               
                 28 
                 97.01 
                 2.99 
                 4.00 
                 Yes (Some) 
                 0.46 
               
               
                 29 
                 95.92 
                 4.08 
                 4.77 
                 Yes (Few) 
                 0.43 
               
               
                 30 
                 95.11 
                 4.89 
                 5.27 
                 None 
                 0.40 
               
               
                 31 
                 93.92 
                 6.08 
                 6.17 
                 None 
                 0.45 
               
               
                   
               
             
          
         
       
     
     Example 6 
     The lens formulation shown in Table 6 were prepared and cured in a manner similar to Example 1. The cured slabs were bulk extracted in acetone. The slabs were then tested for vacuoles and equilibrium water content at 35° C. was determined. The results are shown in Table 6. 
     
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
               
                   
               
               
                   
                 Stock 
                   
                   
                   
                   
                   
               
               
                 For- 
                 Lens 
                   
                   
                   
                   
                 35° C. 
               
               
                 mulation 
                 Solution 
                 Pluronic 
                 Pluronic 
                 Extracts 
                   
                 EWC 
               
               
                 No. 
                 (%) 
                 (Type) 
                 (%) 
                 (%) 
                 Vacuoles 
                 (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 32 
                 100 
                 — 
                 0 
                 2.04 
                 Yes (Full) 
                 0.27 
               
               
                 33 
                 90 
                 L31 
                 10 
                 11.26 
                 Yes (Full) 
                 0.31 
               
               
                 34 
                 90 
                 10R5 
                 10 
                 10.56 
                 Yes (Some) 
                 0.33 
               
               
                   
               
             
          
         
       
     
     Example 7 
     The lens formulations shown in Table 7 were prepared and cured in a manner similar to Example 1. The cured slabs were extracted (bulk) in acetone, tested for vacuoles, inspected for clarity, and equilibrium water content at 35° C. was determined. The results are shown in Table 7. 
     
       
         
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
               
                   
               
               
                   
                 Stock 
                   
                   
                   
                   
                   
                   
               
               
                   
                 Lens 
                   
                   
                   
                   
                   
                 35° C. 
               
               
                 Formulation 
                 Solution 
                 Pluronic 
                 Pluronic 
                 Extracts 
                   
                   
                 EWC 
               
               
                 No. 
                 (%) 
                 (type) 
                 (%) 
                 (%) 
                 Vaculoes 
                 Clarity 
                 (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 35 
                 89.91 
                 P84 
                 10.09 
                 9.01 
                 Yes (full) 
                 Hazy 
                 1.24 
               
               
                 36 
                 90.02 
                 P104 
                 9.98 
                 8.25 
                 Yes (full) 
                 Clear 
                 1.50 
               
               
                 37 
                 90.00 
                 F87 
                 10.00 
                 7.35 
                 Yes (full) 
                 Clear 
                 2.72 
               
               
                 38 
                 89.99 
                 F88 
                 10.01 
                 &lt;Not soluble&gt; 
                 — 
                 — 
                 — 
               
               
                   
               
             
          
         
       
     
     Example 8 
     The lens formulations shown in Table 8 were prepared and cured in a manner similar to Example 1. The cured slabs were bulk extracted in acetone, tested for vacuoles, inspected for clarity, and equilibrium water content at 35° C. was determined. All samples were also subjected to mechanical property testing to determine tensile strength, strain, and Young&#39;s modulus. The results are shown in Table 8. 
     
       
         
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
               
                   
               
               
                   
                 Stock Lens 
                   
                   
                   
                   
                   
                   
                 Tensile 
                   
                 Young&#39;s 
               
               
                 Formulation 
                 Solution 
                 Pluonic 
                 Pluronic 
                 Extracts 
                   
                   
                 35° C. 
                 Strength 
                   
                 Modulus 
               
               
                 No. 
                 (%) 
                 (Type) 
                 (%) 
                 (%) 
                 Vacuoles 
                 Clarity 
                 EWC (%) 
                 (MPa) 
                 Strain (%) 
                 (MPa) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 39 
                 90 
                 L43 
                 10 
                 10.4 
                 Yes (full) 
                 Slight haze 
                 0.5 
                 7.48 
                 127.9 
                 54.4 
               
               
                 40 
                 90 
                 L61 
                 10 
                 10.0 
                 Yes (full) 
                 Slight haze 
                 0.4 
                 7.61 
                 129.2 
                 52.1 
               
               
                 41 
                 90 
                 L64 
                 10 
                 10.3 
                 Yes (full) 
                 Clear 
                 0.5 
                 7.81 
                 138.6 
                 44.28 
               
               
                 42 
                 90 
                 L81 
                 10 
                 10.0 
                 Yes (full) 
                 Slight haze 
                 0.4 
                 7.62 
                 136.6 
                 47.56 
               
               
                 43 
                 90 
                 L92 
                 10 
                 9.5 
                 Yes (full) 
                 Slight haze 
                 0.7 
                 6.66 
                 129.7 
                 41.07 
               
               
                 44 
                 90 
                 L101 
                 10 
                 9.6 
                 Yes (full) 
                 Hazy 
                 0.7 
                 6.57 
                 127.3 
                 45.08 
               
               
                 45 
                 90 
                 17R2 
                 10 
                 10.3 
                 Yes (full) 
                 Hazy 
                 0.5 
                 6.9 
                 136.7 
                 42.32 
               
               
                 46 
                 90 
                 17R4 
                 10 
                 10.3 
                 Yes (some) 
                 Hazy 
                 1.2 
                 6.66 
                 132.9 
                 39.27 
               
               
                 47 
                 90 
                 25R2 
                 10 
                 10.2 
                 Yes (full) 
                 Hazy 
                 1.2 
                 6.15 
                 128.7 
                 37.5 
               
               
                 48 
                 90 
                 31R1 
                 10 
                 9.7 
                 Yes (full) 
                 Hazy 
                 0.9 
                 6.76 
                 133.4 
                 39.82 
               
               
                 49 
                 90 
                 P104 
                 10 
                 8.4 
                 Yes (full) 
                 Clear 
                 1.4 
                 4.77 
                 122 
                 18.69 
               
               
                   
               
             
          
         
       
     
     Example 9 
     The lens formulations shown in Table 9 were prepared and cured in a manner similar to Example 1. The cured slabs were bulk extracted in acetone, tested for vacuoles and equilibrium water content at 35° C. The samples were also subjected to mechanical property testing to determine stress, strain and Young&#39;s modulus values. The results are shown in Table 9. 
     
       
         
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 9 
               
             
             
               
                   
                   
               
               
                   
                 FORMULATION NO. 
               
             
          
           
               
                   
                 50 
                 51 
                 52 
                 53 
                 54 
                 55 
                 56 
                 57 
                 58 
                 59 
                 60 
               
               
                   
                   
               
             
          
           
               
                 PEA 
                 89.52 
                 88.28 
                 86.70 
                 86.41 
                 83.35 
                 84.51 
                 81.80 
                 81.43 
                 78.29 
                 79.49 
                 65.0 
               
               
                 PEMA 
                 9.96 
                 9.98 
                 10.10 
                 12.47 
                 14.91 
                 14.97 
                 15.06 
                 17.49 
                 19.95 
                 19.97 
                 30.0 
               
               
                 BDDA 
                 0.52 
                 1.74 
                 3.20 
                 1.12 
                 1.74 
                 0.52 
                 3.15 
                 1.08 
                 1.76 
                 0.54 
                 3.20 
               
               
                 Pluronic 25R4 
                 9.22 
                 9.19 
                 9.14 
                 9.17 
                 9.07 
                 9.12 
                 9.11 
                 9.10 
                 9.06 
                 9.42 
                 — 
               
               
                 Perkadox 16S 
                 2.00 
                 2.00 
                 2.01 
                 2.00 
                 1.99 
                 1.99 
                 2.01 
                 1.99 
                 2.01 
                 2.00 
                 1.80 
               
               
                 Extracts (%) 
                 10.04 
                 8.71 
                 7.67 
                 8.90 
                 8.59 
                 9.77 
                 7.55 
                 8.93 
                 8.51 
                 9.98 
                 2.00 
               
               
                 Vacuoles 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 Yes (Full) 
               
               
                 35° C. EWC 
                 0.63 
                 0.60 
                 0.84 
                 0.52 
                 0.66 
                 0.58 
                 0.83 
                 0.53 
                 0.50 
                 0.57 
                 0.35 
               
               
                 Stress (MPa) 
                 3.59 
                 4.00 
                 2.79 
                 4.34 
                 4.49 
                 3.61 
                 3.79 
                 4.64 
                 5.14 
                 4.63 
                 8.65 
               
               
                 Strain (%) 
                 297 
                 166 
                 102 
                 214 
                 167 
                 291 
                 113 
                 216 
                 169 
                 299 
                 100 
               
               
                 Young&#39;s 
                 3.17 
                 4.06 
                 5.03 
                 4.08 
                 4.79 
                 4.02 
                 6.44 
                 5.23 
                 6.1 
                 5.35 
                 68.8 
               
               
                 Modulus 
               
               
                 (MPa) 
               
               
                   
               
             
          
         
       
     
     Example 10 
     The formulations shown in Table 9 were tested for microvacuoles five days after they were prepared and the results are shown in Table 10. All samples were vacuole-free. The samples were stored in water at room temperature for one year and then visually inspected. These results are also shown in Table 10. 
     
       
         
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 10 
               
             
             
               
                   
                   
               
               
                   
                 FORMULATION NO. 
               
             
          
           
               
                   
                 60 
                 50 
                 55 
                 59 
                 57 
                 53 
                 51 
                 54 
                 58 
                 56 
                 52 
               
               
                   
                   
               
             
          
           
               
                 X-linker 
                 3.20 
                 0.52 
                 0.52 
                 0.54 
                 1.08 
                 1.12 
                 1.74 
                 1.74 
                 1.76 
                 3.15 
                 3.20 
               
               
                 concentration 
               
               
                 Vacuoles @ 
                 Yes 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
                 None 
               
               
                 5 days 
                 (Full) 
               
               
                 Visual 
                 — 
                 Haze 
                 Haze 
                 Haze 
                 Haze 
                 Haze 
                 Haze 
                 Haze 
                 Haze 
                 Clear 
                 Clear 
               
               
                 Inspection @ 
               
               
                 1 year 
               
               
                   
               
             
          
         
       
     
     The invention having now been fully described, it should be understood that it may be embodied in other specific forms or variations without departing from its spirit or essential characteristics. Accordingly, the embodiments described above are to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.