Role of Silicon Contamination on Calcification of Hydrophilic Acrylic Intraocular Lenses

Role of Silicon Contamination on Calcification of Hydrophilic Acrylic Intraocular Lenses LILIANA WERNER, MD, PHD, BRIAN HUNTER, MD, SCOTT STEVENS, MD, JESSE J.L. CHEW, MD, FRCSC, AND NICK MAMALIS, MD

● PURPOSE:

To verify the presence of the element silicon on hydrophilic acrylic intraocular lenses (IOLs) explanted because of calcification. ● DESIGN: Interventional case series with clinicopathological correlation. ● METHODS: Twenty explanted IOLs with surface deposits (MemoryLens), and 20 with deposits mostly within their optic substance (SC60B-OUV and Aqua-Sense; 10 each) were used. After gross, microscopic, and histochemical analyses to confirm the presence of deposits, the lenses underwent scanning electron microscopy (SEM) with energy dispersive x-ray spectroscopy (EDS) for elemental composition, on the external surface of MemoryLens IOLs, and on the surface and internal substance of SC60B-OUV and Aqua-Sense IOLs. The weight percentage of the element silicon was obtained at the level of deposits, and at adjacent deposit-free areas in all lenses. ● RESULTS: Scanning electron microscopy (SEM) coupled with EDS confirmed that the composition of the deposits was calcium/phosphate in all cases. The element silicon was found in all 40 lenses, on all areas analyzed. The silicon weight percentage was higher at the level of the deposits. The presence of aluminum on five MemoryLens IOLs, and in most of the SC60B-OUV and Aqua-Sense lenses might be related to scattering from the aluminum mounting stubs used for surface analyses. ● CONCLUSIONS: Silicone compounds have been implicated in the calcification of another hydrophilic acrylic design (Hydroview). They may also have a role in the calcification of other hydrophilic acrylic IOLs. Further investigation on the relationship between the presence of the element silicon and the silicone compounds found on calcified hydrophilic acrylic lenses is necessary. (Am J

Accepted for publication Aug 22, 2005. From the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. Supported by the Research to Prevent Blindness Olga Keith Wiess Scholar Award (to Liliana Werner, MD, PhD). Presented in part as a paper at the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Washington, DC, April 2005. Inquiries to Liliana Werner, MD, PhD, John A. Moran Eye Center, University of Utah, 50 North Medical Drive, Salt Lake City, UT 84132; fax: (801) 581 3357; e-mail: [email protected] 0002-9394/06/$32.00 doi:10.1016/j.ajo.2005.08.045

©

2006 BY

Ophthalmol 2006;141:35– 43. © 2006 by Elsevier Inc. All rights reserved.)

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INCE NOVEMBER 1999, OUR LABORATORY HAS RE-

ceived intraocular lenses (IOLs) manufactured from different copolymers of hydrophilic acrylic that had been explanted because of opacification of their optic component caused by calcified deposits (calcification). The four major designs involved in the process were the Hydroview (Bausch and Lomb, Rochester, New York),1– 6 the MemoryLens (CibaVision, Duluth, Georgia),7,8 the SC60B-OUV (Medical Developmental Research, Clearwater, Florida),9 –13 and the Aqua-Sense (Ophthalmic Innovations International, Ontario, California).14,15 In the case of the Hydroview and the MemoryLens, the calcified deposits were generally found on the external optic surfaces of the lenses, while with the other two designs, the calcified deposits were mostly intra-optic. Investigations performed by the manufacturer of the Hydroview lens suggest that calcium deposits formed on the surface of the optic in the presence of free fatty acids and silicone compounds, the latter migrating to the IOL surface from the gasket used to seal the packaging vial (SureFold System, Bausch and Lomb, Rochester, New York).16 Silicone compounds were found on the surfaces of never-implanted Hydroview lenses taken from the SureFold packaging, in surface analyses for molecular composition (Guttman C, “Hydroview calcification resolved”. Ophthalmology Times, 2001;26:4). More recently, Dorey and associates analyzed 17 explanted Hydroview lenses and demonstrated the presence of the element silicon mainly at the center of the calcified deposits, in surface analyses for elemental composition (silicon refers to the element, while silicone refers to polymers with an Si-O backbone).6 The element silicon appears to be physiologically localized in high concentrations in specific portions of tissues associated with calcification, such as bone.17 Therefore, the aim of our study was to assess the presence of the element silicon in relation to calcified deposits observed with the other three major hydrophilic acrylic IOL designs involved in the process of calcification.

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TABLE 1. Summary of the Characteristics of the Cases With Calcification of Hydrophilic Acrylic Intraocular Lenses Included in This Study

IOL Design

Age of Patients at Implantation (yrs)

Date of Explantation

Time to Explantation (mos)

MemoryLens (N ⫽ 20)

73.13 ⫾ 11.32

From 07/10/01 to 12/11/02

30.00 ⫾ 5.16

SC60B-OUV (N ⫽ 10) Aqua-Sense (N ⫽ 10)

72.75 ⫾ 7.75 67.91 ⫾ 17.61

From 07/21/00 to 10/29/01 From 04/10/01 to 11/11/02

20.22 ⫾ 11.02 16.27 ⫾ 6.45

Associated Conditions

Diabetes (N ⫽ 8); hypertension (N ⫽ 5); hyperthyroidism (N ⫽ 1); gout (N ⫽ 1); arthritis (N ⫽ 1); glaucoma (N ⫽ 4); macular hole (N ⫽ 1) Diabetes (N ⫽ 2); macular pucker (N ⫽ 1) Diabetes (N ⫽ 4); hypertension (N ⫽ 4); asthma (N ⫽ 1); age-related macular degeneration (N ⫽ 2); history of macular pucker/retinal detachment (N ⫽ 1)

IOL ⫽ intraocular lens.

FIGURE 1. Surface analyses performed on the hydrophilic acrylic lenses. (Left) Scanning electron photomicrograph from the surface of a MemoryLens, which had zones with multi-layered deposits of various sizes and shapes. The square delimitates the deposit area where energy dispersive x-ray spectroscopy was performed. (Middle) Spectrum displaying peaks corresponding to the different elements present within the area shown in the photomicrograph. Carbon (C) and oxygen (O) are normal components of the lens optic material. The high peaks of phosphate (P) and calcium (Ca) confirm the calcified nature of the surface deposits. (Right) Table showing the weight percentage of the different elements displayed in the spectrum. Note the presence of the element silicon, corresponding to the Si peak displayed in the spectrum.

associated with a decrease in the visual function in each case. The explanted IOLs were sent to our center in the dry state, or in vials containing a balanced salt solution. For each explant, gross examination was performed and gross pictures were taken using a Nikon digital camera (Model D1x with a Nikon ED 28 –70 mm AF lens, Nikon, Tokyo, Japan). The unstained lenses were then microscopically evaluated and photographed under a light microscope

METHODS INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE AP-

proval was not required for this study. Table 1 summarizes the characteristics of the explantation cases included in this study. In all instances, the lenses were fixated in the capsular bag, after uneventful phacoemulsification. Each lens was explanted because of optic opacification, noted during the first or second year after implantation. This was 36

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FIGURE 2. MemoryLens opacification. (Top left) Slit-lamp photograph showing a patient implanted with a MemoryLens, which exhibited optic opacification (courtesy of Dr Alan Crandall, USA). (Top right) Gross photograph showing a thin granularity covering the optic surfaces of the explanted MemoryLens. The calcified nature of the surface deposits was suggested by histochemical methods for calcium (alizarin red, bottom left, original magnification ⴛ200; von Kossa method, bottom right, original magnification ⴛ100).

(Olympus, Optical Co Ltd, Tokyo, Japan) to assess the presence of deposits that could be causing the reported opacification in each case. The presence of calcified deposits on the surface and/or within the substance of the lenses was further assessed by one or both of the following histochemical methods (according to techniques already described in previous publications): alizarin red stain, or the von Kossa method.1,2 The lenses were then sent to D. Zhao, PhD (Electron Microscopy Center of the University of South Carolina, Columbia, South Carolina). They were air-dried at room temperature for at least 3 days, mounted uncoated on a carbon sticky tape on a round sample aluminum stub for imaging, and analyzed using an environmental scanning electron microscopy (SEM) (FEI Quanta 2000 ESEM, Hillsboro, Oregon), equipped with an energy dispersive x-ray spectroscopy (EDS) detector with light element capabilities. After areas of significant deposition were located by SEM, EDS point spectra were acquired with the same acquisition conditions for the deposits, and depositfree areas, adjacent to the deposits. In the case of the VOL. 141, NO. 1

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MemoryLens, each lens was bisected, and SEM and EDS were performed on the surface of one-half of the lens. In the case of the SC60B-OUV and Aqua-Sense lenses, each lens was bisected and at least one cylindrical block passing through the optic was obtained by two full thickness sections. SEM and EDS were then performed on the surface of one-half of the lens, and on the internal face of the cylindrical block (internal optic substance). EDS analyses focused on the presence of calcium (Ca) and phosphate (P) peaks, in order to confirm the calcified nature of the deposits, and also on the presence of silicon (Si) peaks. For each specimen, sets of a high magnification SEM photomicrograph showing areas of interest, a graph displaying the peaks obtained at the same areas, and a table with the value of weight percentage of each element corresponding to the graph were obtained from areas with and without deposits (Figure 1). Control lenses, explanted because of reasons other than optic opacification, were also prepared and analyzed for SEM and EDS. Poly (methyl methacrylate) (PMMA) (N ⫽ 3), hydrophobic acrylic (N ⫽ 3), and silicone AND

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FIGURE 3. SC60B-OUV lens opacification. (Top left) Slit-lamp photograph showing a patient implanted with a SC60B-OUV lens, which exhibited optic opacification (courtesy of Dr Mahmut Kaskaloglu, Turkey). (Top right) Gross photograph showing opacification of the most central optic area of the explanted SC60B-OUV, with a clear optic edge and clear haptics. The calcified nature of the deposits mostly present within the optic was suggested by histochemical methods for calcium (alizarin red, bottom left, original magnification ⴛ100; von Kossa method, bottom right, original magnification ⴛ40). The arrow shows the actual optic edge of the lens.

lenses (N ⫽ 4), explanted because of pseudophakic bullous keratopathy, dislocation, or during evisceration were used as controls. The rigid, PMMA lenses were not sectioned, while the foldable lenses were sectioned as described above. Hydrophilic acrylic lenses of the same three designs evaluated in this study, explanted because of reasons other than postoperative opacification were not available to be used as controls in this study. Neverimplanted lenses of the same three designs, from the same lots that were associated with calcification could also not be obtained to be used as controls.

mostly found within the substance of the lens optic, in a line delineating the external optic surface. A clear margin was present between the internal optic deposits and the external surface. The haptics of these lenses were in general clear. The presence of deposits was found on the external surfaces of the optic and haptics of the AquaSense lenses, which were practically in continuation with deposits within their internal substance. The above mentioned deposits with the three lens designs stained positive with the histochemical methods for calcium (alizarin red and the von Kossa method) (Figures 2, 3, and 4). Scanning electron microscopy coupled with EDS demonstrated that the deposits opacifying the three lens designs in each case were at least in part composed of calcium (Ca) and phosphate (P). Table 2 shows the weight percentage of the element silicon from spectra obtained at the external optic surface of the MemoryLens IOLs (at the deposits and at adjacent deposit-free areas), and from spectra obtained at the external and internal optic surfaces of the SC60B-OUV and Aqua-Sense lenses (also at the deposits and at adjacent deposit-free areas, in each sur-

RESULTS GROSS AND MICROSCOPIC EVALUATION CONFIRMED THE

presence of deposits, causing the optic opacification observed in each explant. In the case of the MemoryLens, the deposits were found only on the external surfaces of the lenses’ optics, and in general presented as multiple, small granules. Few deposits were found on the external surfaces of the optics of the SC60B-OUV lenses. The deposits were 38

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FIGURE 4. Aqua-Sense opacification. (Top left) Slit-lamp photograph showing a patient implanted with an Aqua-Sense lens, which exhibited optic opacification (courtesy of Drs Mark Batterbury and Aby Jacob, UK). (Top right) Gross photograph showing opacification of the optic and haptic components of the lens. The calcified nature of the deposits found on the surface and within the lens was suggested by histochemical methods for calcium (alizarin red, bottom left, original magnification ⴛ40; von Kossa method, bottom right, original magnification ⴛ100).

TABLE 2. Means ⫾ Standard Deviations of the Weight Percentage (WT%) for the Element Silicon (Si) Obtained on the External Surface and Internal Substance of the Explanted Lenses Analyzed

IOL Design

WT%, External Surface (Deposits)

WT%, External Surface (Outside Deposits)

WT%, Internal Substance (Deposits)

WT%, Internal Substance (Outside Deposits)

MemoryLens (N ⫽ 20) SC60B-OUV (N ⫽ 10) Aqua-Sense (N ⫽ 10)

0.34 ⫾ 0.57 0.42 ⫾ 0.92 0.18 ⫾ 0.21

0.08 ⫾ 0.04 0.21 ⫾ 0.43 0.08 ⫾ 0.08

Not analyzed 0.09 ⫾ 0.03 0.11 ⫾ 0.07

Not analyzed 0.05 ⫾ 0.01 0.06 ⫾ 0.03

IOL ⫽ intraocular lens.

face). It is noteworthy that the presence of the element silicon was found in all spectra obtained at the different areas, in all 40 explants analyzed. The weight percentage of the element silicon appeared to be higher at the level of the calcified deposits, in comparison to the adjacent deposit-free areas, on the external and internal surfaces of VOL. 141, NO. 1

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the lenses (with the exception of the internal surface of the MemoryLens IOLs, which was not analyzed). The presence of the element aluminum was also found in five MemoryLens IOLs, as well as in most of SC60BOUV and Aqua-Sense lenses analyzed (mostly in the analyses of the internal surface of the cylindrical blocks). AND

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SEM coupled with EDS analyses of the control lenses showed the presence of the element silicon on the external surface of only one PMMA lens (weight percentage ⫽ 0.18). The element silicon was not found on or within the hydrophobic acrylic lenses. The control silicone lenses were not considered for this analysis, as this element is a normal component of the silicone material. The presence of the element aluminum was not found in analyses of rigid, PMMA lenses. This was only associated with foldable lenses, which had been sectioned for analysis of the internal optic surface of cylindrical blocks. Aluminum was found on the external (weight percentage, 0.35 ⫾ 0.08) and internal (weight percentage, 0.32 ⫾ 0.03) surfaces of three control silicone lenses, and on the internal surface of three control AcrySof lenses (weight percentage, 0.20 ⫾ 0.16).

To the best of our knowledge, the calcification cases with the MemoryLens and the SC60B-OUV have not previously been related to silicone compounds. In 1999, episodes of sterile hypopyon associated with implantation of the MemoryLens were reported.18 Following these reports, in April 2000, Ciba Vision announced a worldwide recall of certain lots of the MemoryLens models U940A and U940S. A possible causative factor was a polishing residual (aluminum oxide) found on the surface of the concerned lenses. Reports on “clouding” of the same designs also started in 1999. As of March 2004, we have analyzed 106 MemoryLens IOLs, explanted because of late postoperative opacification.7,8 The mean time interval between the initial cataract surgery and the diagnosis of lens opacification was 25.8 ⫾ 11.9 months (range, 3.3 to 80.7 months). The manufacturer correlated the opacification of this design with a change in the polishing process in 1999. The modified manufacturing method used a phosphate buffer in the tumbling process, which would attract more protein. The process would then continue to progress with the deposition of minerals, most likely calcium, on top of the protein film. According to the manufacturer, the recall in April 2000 (associated with the cases of sterile hypopyon) also included all MemoryLens IOLs manufactured using the modified tumbling process. Ciba Vision then changed the polishing process and reintroduced the MemoryLens in October 2000 with the models U940S and CV232, the latter featuring a square optic-edge design.8 Since 1999, we have analyzed 59 explanted SC60BOUV IOLs (Medical Developmental Research, Clearwater, Florida) in our laboratory and demonstrated the presence of calcified deposits mostly within the optic of the lenses.10 –15 The analyses of Frohn and associates on 41 SC60B-OUV IOLs indicated premature aging of the ultraviolet blocking agent within the lenses, the source of the opacification being a change in the IOL material itself.19 Medical Developmental Research (now EyeKon Medical, Clearwater, Florida) changed their polymer supplier, and currently manufactures different hydrophilic acrylic designs, including the SC25-Fold lens, which has recently received Food and Drug Administration approval for clinical investigation in the United States. Similar to the study by Dorey and associates on explanted Hydroview lenses,6 we demonstrate for the first time the presence of the element silicon in relation to calcified deposits with the three other major hydrophilic acrylic designs that have been associated with calcification. While Dorey and associates used EDS attached to a transmission electron microscope, we used and EDS system attached to an environmental SEM. Both techniques provide the same kind of information on the elemental composition of deposits. However, the environmental SEM we used did not require any fixation, embedding, or coating of the specimens. The element silicon was detected in all areas analyzed, in all lenses, with a weight percentage higher at the level of the deposits in compari-

DISCUSSION IN 1997, BAUSCH AND LOMB CHANGED THE HYDROVIEW

lens packaging system to incorporate the SureFold holder/ folder. In May 1999, the manufacturer first received reports about “clouding” of these lenses. Since November 1999, our center has received 40 explanted Hydroview lenses for pathological analyses. The interval between the cataract procedure and the time the opacification of the lenses in our series was noted ranged from 5 to 48 months (19.75 ⫾ 11.88).1,2,13–15 Surface chemistry studies of explanted Hydroview lenses performed by Bausch and Lomb identified the lens deposits as a layered mixture of octacalcium phosphate, fatty acids, salts, and small amounts of silicone compounds. As the silicone gasket sealing the new SureFold cap was the only difference in the manufacturing and packaging of the lenses, this gasket came under suspicion early. The manufacturer has since changed the packaging of the Hydroview, which is now sealed with a gasket made from a perfluoroelastomer (Green G, et al. An issue resolved. The Hydroview intraocular lens: development, early reports of calcification, and subsequent actions. White paper. Bausch and Lomb; July 29, 2003). The calcification problem with the Aqua-Sense design has also been associated with silicone compounds. Since the beginning of 2001, we have received 21 Aqua-Senses lenses in our laboratory.14,15 Ophthalmic Innovations International stated that researchers, using x-ray photoelectron spectroscopy surface analysis, have found trace siloxane species on the surfaces of the opacified lenses. These siloxane compounds were hypothesized to have come from the silicone elastomer packaging components used at that time. These packaging components have since been removed and changed to non-silicone materials (Robert Sheehan, Vice President of Regulatory Affairs and Quality Systems, Ophthalmic Innovations International, personal communication, April, 2001). 40

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son to the adjacent, deposit-free areas. Dorey and associates found the element silicon mostly within the center of the deposits in 14 out of 17 explants. It has to be highlighted that the analyses done by the manufacturers of the Hydroview and Aqua-Sense designs give information at the molecular level. The contamination with those designs was in the form of low molecular weight silicone compounds forming a thin fluid film (although it is referred as “particles” in some publications). These kinds of techniques (for example, x-ray photoelectron spectroscopy, and surface mass spectroscopy) sample the top 75 Angstroms of a surface, against 1000 to 50,000 Angstroms sampled by EDS. The term weight percentage of an element, used to describe the presence of the silicon element in our current study, is actually a measurement of a volume element at one spot only. Therefore, EDS analyses are probably more useful to describe particulate forms of contamination, instead of a silicone monolayer.20,21 It is also important to differentiate the terms silicone and silica. This latter is represented by compounds of silicon dioxide (SiO2) generally seen as glass or quartz, whereas silicone compounds are in forms that vary from liquid (oils) to hard rubber. As the presence of the silicon element may be an artifact either from glassware contamination, or from small dust particles (for example, clays), we processed lenses explanted because of other reasons than calcification in the same manner as the calcified lenses. Out of three PMMA and three hydrophobic acrylic lenses, the presence of the element silicon was found on the external surface of only one PMMA lens. This element was not found on the external surface or the internal substance of the hydrophobic acrylic lenses. Therefore, we believe that the presence of the element silicon on the external surface of the three major hydrophilic acrylic designs analyzed here may have a role in their calcification process. The element silicon was also found on the internal substance of the SC60BOUV and Aqua-Sense lenses. However, we cannot exclude the possibility that this may be related to the act of sectioning the lenses, and, therefore, dragging surface particles along the cut line. It is also noteworthy that the element aluminum is often detected on samples because of scattering from the aluminum mounting stub. Its presence was indeed mostly detected in the analyses of the cylindrical optic blocks, with a smaller surface area than the one-half of the lenses used for the analyses of the external surface. Previous studies demonstrated that highly hydrated silica surfaces are effectively catalytic for calcium/phosphate nucleation.22–25 The element silicon was found to have a role in bone calcification. A high level of silicon in the uncalcified osteoid region of young bone is thought to provide a number of SiOH groups for initiating calcium phosphate formation. Heterogeneous nucleation of apatite can be induced from metastable calcium phosphate solutions, including physiologic fluids on those specific surfaces of materials, where there VOL. 141, NO. 1

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are abundant acidic OH groups. Li and associates implanted plugs made of a porous sol-gel-prepared silica into the femurs of goats.23 The authors demonstrated that a calcium phosphate mineralization was formed both on the silica plugs and within the pores inside the plugs, 12 weeks postoperatively. Stein and associates demonstrated that there may be a role for the element silicon in ectopic calcification of cardiac valves.24 They analyzed 97 surgically excised natural cardiac valves by SEM coupled with EDS. Crystalline deposits that contained the element silicon were associated with 34 of 97 of these valves. Among the 34 valves that showed the presence of silicon, 24 also showed microdeposits of calcific material. Dieudonne and associates performed primary cultures of osteogenic precursor cells derived from rat bone marrow stroma on titanium disks, and on silica gel bioactive glass disks.25 The cultures performed on the latter displayed a substantially higher differentiating capacity for both osteogenic cell markers, as well as in vitro mineralization, in comparison with the titanium substrates. However, the element silicon alone cannot induce calcification and other factors are probably involved. Also, calcification has not been associated with IOLs manufactured from silicone materials. There are only few cases in the literature describing calcification on the posterior surface of silicone lenses, in eyes with asteroid hyalosis.26 –28 Guan and associates have recently published their results using the model constructed for analysis of the calcification process with the Hydroview lens.16 The authors evaluated the role of long-chain saturated fatty acids present in the aqueous humor (myristic, palmitic, stearic, arachidic, and behenic) on the process. The IOLs (Hydroview) were exposed to cyclic silicone compounds, and treated with one of the above mentioned fatty acids, at different concentrations. Then, they were rinsed and placed in supersaturated solutions of calcium chloride and potassium dihydrogen phosphate. They demonstrated that the fatty acids cannot bind directly to the IOL surfaces and, therefore, can also not induce calcification by themselves. However, hydrophobic cyclic silicone compounds adsorbed at the IOL surfaces interacted strongly with the hydrophobic carbon chains of the fatty acids, to create a layer of fatty acids oriented with polar, functional hydrophilic groups exposed to the aqueous solution, providing nucleation sites for calcium/phosphate. Fatty acids with shorter chains were more readily adsorbed at the IOLcyclic silicone surfaces, resulting in shorter nucleation induction times. Nucleation was also promoted by increasing the concentration of the fatty acids used. Furthermore, the same authors evaluated the effects of precoating of the Hydroview with different ophthalmic viscosurgical devices (OVDs), and determined that they displayed different calcification properties.16 Whether or not this is correlated with the findings of Ohrstrom and associates, that small AND

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5. Oner HE, Durak I, Saatci OA. Late postoperative opacification of hydrophilic acrylic intraocular lenses. Ophthalmic Surg Lasers 2002;33:304 –308. 6. Dorey MW, Brownstein S, Hill VE, et al. Proposed pathogenesis for the delayed postoperative opacification of the hydroview hydrogel intraocular lens. Am J Ophthalmol 2003;135:591–598. 7. Tehrani M, Mamalis N, Wallin T, et al. Late postoperative opacification of MemoryLens hydrophilic acrylic intraocular lenses: case series and review. J Cataract Refract Surg 2004;30:115–122. 8. Neuhann IM, Werner L, Izak AM, et al. Late postoperative opacification of a hydrophilic acrylic (hydrogel) intraocular lens: a clinicopathological analysis of 106 explants. Ophthalmology 2004;111:2094 –2101. 9. Chang BYP, Davey KG, Gupta M, Hutchinson C. Late clouding of an acrylic intraocular lens following routine phacoemulsification (Letter). Eye 1999;13:807– 808. 10. Werner L, Apple DJ, Kaskaloglu M, Pandey SK. Dense opacification of the optical component of a hydrophilic intraocular lens: a clinicopathological analysis of nine explanted lenses. J Cataract Refract Surg 2001;27:1485–1492. 11. Pandey SK, Werner L, Apple DJ, Kaskaloglu MM. Hydrophilic acrylic intraocular lens optic and haptics opacification in a diabetic patient: bilateral case report and clinicopathological correlation. Ophthalmology 2002;109:2042–2051. 12. Macky TA, Werner L, Soliman MM, et al. Opacification of two hydrophilic acrylic intraocular lenses 3 months after implantation. Ophthalmic Surg Lasers Imaging 2003;34:197–202. 13. Werner L, Apple DJ. Complications of aphakic and refractive intraocular lenses. International Ophthalmology Clinics. Philadelphia: Lippincott Williams and Wilkins, 2001: 41(3). 14. Werner L, Apple DJ, Izak AM. Discoloration/opacification of modern foldable hydrogel intraocular lens designs. In: Buratto L, Werner L, Zanini M, Apple DJ, editors. Phacoemulsification: principles and techniques. Thorofare: Slack Inc, 2003:659 – 670. 15. Izak AM, Werner L, Pandey SK, Apple DJ. Calcification of modern foldable hydrogel intraocular lens designs. Eye 2003; 17:393– 406. 16. Guan X, Tang R, Nancollas GH. The potential calcification of octacalcium phosphate on intraocular lens surfaces. J Biomed Mater Res 2004;71A:488 – 496. 17. Carlisle EM. Silicon: a possible factor in bone calcification. Science 1970;167:279 –280. 18. Jehan FS, Mamalis N, Spencer TS, et al. Postoperative sterile endophthalmitis (TASS) associated with the MemoryLens. J Cataract Refract Surg 2000;26:1773–1777. 19. Frohn A, Dick B, Augustin AJ, Grus FH. Late opacification of the foldable hydrophilic acrylic lens SC60B-OUV. Ophthalmology 2001;108:1999 –2004. 20. Srnova-Sloufova I, Vlckova B, Bastl Z, Hasslett TL. Bimetallic (Ag)Au nanoparticles prepared by the seed growth method: two-dimensional assembling, characterization by energy dispersive x-ray analysis, x-ray photoelectron spectroscopy, and surface enhanced raman spectroscopy, and proposed mechanism of growth. Langmuir 2004;20:3407–3415. 21. Shahwan T, Zunbul B, Tunusoglu O, Eroglu AE. AAS, XRPD, SEM/EDS, and FTIR characterization of Zn(2⫹) retention by calcite, calcite-kaolinite, and calcite-clinoptilolite minerals. J Colloid Interface Sci 2005;286:471– 478.

amounts of silicone oil is a common contaminant of these solutions requires further investigation.29 The MemoryLens is packaged in a glass vial with balanced salt solution. According to the manufacturer, the roller-retainer in which the lens is placed is of polycarbonate. The lens is protected by a thin Teflon film, and the white cover is of silicone rubber. Mattová and associates analyzed two MemoryLens IOLs explanted because of calcification, and compared it to a never-implanted lens of the same design.30 The authors could not demonstrate the presence of silicone compounds on any of the lenses by infrared spectral analysis. However, they postulated that initial contact of the lenses with alcohol during histopathologic examination could eventually be responsible for that. Interestingly, the same study showed the presence of UV absorber in the extracts from the never-implanted lens, but not in extracts from the opacified lenses. This latter had increased concentration of low-molecular-weight components, normally generated during polymer degradation. We could not obtain information on the presence of silicone components in the packaging of the SC60BOUV lenses from the lots that were related to the calcification problem. Similarly, we could not obtain nonimplanted lenses from the same lots of the three designs used in this study, to be used as controls, as they were recalled. Further studies are necessary to investigate the possible sources of silicon contamination onto IOLs, as EDS cannot distinguish between silicone and silica. It is also necessary to further investigate the relationship between our results and the silicone compounds found on two IOL designs (Hydroview and Aqua-Sense) by analyses done at the molecular level, as well as the combination of factors leading to IOL calcification.20 ACKNOWLEDGMENT

Donggao Zhao, PhD (Electron Microscopy Center, University of South Carolina, Columbia, South Carolina), provided assistance with surface analysis.

REFERENCES 1. Werner L, Apple DJ, Escobar-Gomez M, et al. Postoperative deposition of calcium on the surfaces of a hydrogel intraocular lens. Ophthalmology 2000;107;2179 –2185. 2. Pandey SK, Werner L, Apple DJ, Gravel JP. Calcium precipitation on the optical surfaces of a foldable intraocular lens: a clinicopathological correlation. Arch Ophthalmol 2001;120:391–393. 3. Yu AKF, Kwan KYW, Chan DHY, Fong DYT. Clinical features of 46 eyes with calcified hydrogel intraocular lenses. J Cataract Refract Surg 2001;27:1596 –1606. 4. Habib NE, Freegard TJ, Gock G, et al. Late surface opacification of Hydroview intraocular lenses. Eye 2002;16:69 –74.

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22. Leyva AG, Maguid SL, Rodriguez de Benyacar AR, et al. Pathological mineralizations: Calcifications and Si-bearing particles in soft tissues and their eventual relationship to different prostheses. Artif Organs 2000;24:179 –181. 23. Li P, Ye X, Kangasniemi I, et al. In vivo calcium phosphate formation induced by sol-gel-prepared silica. J Biomed Mater Res 1995;29:325–328. 24. Stein PD, Wang CH, Riddle JM, et al. Deposits of crystalline material containing silicon in surgically excised human valves. J Lab Clin Med 1990;116:711–716. 25. Dieudonne SC, van den Dolder J, de Ruijter JE, et al. Osteoblast differentiation of bone marrow stromal cells cultured on silica gel and sol-gel-derived titania. Biomaterials 2002;23:3041–3051. 26. Werner L, Kollarits CR, Mamalis N, Olson RJ. Surface calcification of a three-piece silicone intraocular lens in a

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patient with asteroid hyalosis: a clinicopathologic case report. Ophthalmology 2005;112:447– 452. Wackernagel W, Ettinger K, Weitgasser U, et al. Opacification of a silicone intraocular lens caused by calcium deposits on the optic. J Cataract Refract Surg 2004;30: 517–520. Zhang F, Kamp F, Hamilton JA. Dissociation of long and very long chain fatty acids from phospholipid bilayers. Biochemistry 1996;35:16055–16060. Ohrstrom A, Svensson B, Tegenfeldt S, Celiker C, Lignell B. Silicone oil content in ophthalmic viscosurgical devices. J Cataract Refract Surg 2004;30:1278 –1280. Mattová J, Bohác˘ová E, Murgas˘ová Z, et al. Opacification of hydrophilic MemoryLens U940A intraocular lenses: analysis of two explanted lenses. J Cataract Refract Surg 2004;30: 1934 –1939.

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Biosketch Liliana Werner, MD, PhD, is Assistant Professor of Ophthalmology at the Moran Eye Center, University of Utah, and Director of Research of the David J. Apple, MD Laboratories for Ophthalmic Devices Research. She has an MD degree from Brazil, and a PhD degree from France. She is the 2004 Research to Prevent Blindness Olga Keith Wiess Scholar awardee, member of the Editorial Board of the JCRS and the EyeWorld magazine, and member of the International Intra-Ocular Implant Club.

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