Late opacification of the foldable hydrophilic acrylic lens SC60B-OUV

Late Opacification of the Foldable Hydrophilic Acrylic Lens SC60B-OUV Andreas Frohn, MD,1 H. Burkhard Dick, MD,2 Albert J. Augustin, MD,2 Franz H. Grus, MD, PhD2 Objective: To investigate the cause of severe central opacification in 41 foldable acrylic intraocular lenses (IOLs) requiring explantation. Another IOL was opacified in the original sealed vial. Design: Case series and laboratory analysis. Testing: Light microscopy, high performance liquid chromatography, sodium dodecyl sulfate polyacoylamide gel electrophoresis, spectrometric analysis, and autoclaving. Results: Neither fatty acids nor proteins could be identified within the IOLs. Spectrometric analysis yielded absorption peaks in the ultraviolet spectral range. Conclusions: The spectroscopic findings indicate premature aging of the ultraviolet blocking agent. The source of the opacification is a change in the IOL material itself. Ophthalmology 2001;108:1999 –2004 © 2001 by the American Academy of Ophthalmology. Both polymethyl methacrylate (PMMA) and 2-hydroxyethyl-methacrylate (PHEMA) have been used in the field of medical devices for contact lenses or intraocular lenses (IOLs) for a number of years. Because of the increasing acceptance of small-incision cataract surgery and foldable IOLs, hydrophilic acrylic lenses are becoming more popular. There are different types of foldable acrylic IOL materials. All variations belong to the composition of the copolymers and minor alterations of the side chains; the addition of PMMA to PHEMA yields a polymer with a lower water content, hence a higher refractive index, and improved strength. The polymerization of this combination of materials must control this natural incompatibility to ensure formation of a random polymer and to avoid domain formation that may affect clarity and therefore optical quality. Thus, the polymer backbone gives each IOL different physical and biologic properties.1 At the end of the last decade, Medical Developmental Research (St. Petersburg, FL) released a new hydrophilic acrylic IOL. The lens type was called SC60B-OUV. The haptics are modified C-loops molded from the same material as the optic, providing a one-piece design with an optical zone of 6.0 mm. The IOLs were manufactured from a copolymer consisting of hydrophobic PMMA and hydrophilic PHEMA with a water content of 26%. An ultraviolet (UV) blocking agent is included in the material to protect the eye from UV-A, UV-B, and UV-C radiation. The comOriginally received: August 7, 2000. Accepted: June 4, 2001. Manuscript no. 200471. 1 University Eye Hospital Tuebingen, Tuebingen, Germany. 2 University Mainz, Department of Ophthalmology, Mainz, Germany. Presented in part at the congress of the American Society of Cataract and Refractive Surgery, Boston, Massachussetts, May 2000. None of the authors has any proprietary or financial interest in any object mentioned in this study. Correspondence to Andreas Frohn, MD, Sandstr 47, D-57072 Siegen, Germany. E-mail: [email protected]. © 2001 by the American Academy of Ophthalmology Published by Elsevier Science Inc.

position of the UV blocker is not provided and usually is of a proprietary nature. Commonly used UV blockers are derivatives of benzotriazoles or benzophenones. Both of these materials are incorporated into the polymer matrix during polymerization, thus avoiding gradual leaching and loss of effectiveness over time. After introducing this lens and a postoperative observation period of 6 months, we started to implant the SC60BOUV routinely. In the beginning, highly acceptable results were obtained after implantation in single cases. Handling during the surgical procedure, material properties, and initial biocompatibility were convincing. In spring 1999, the first lens developed a gray-whitish opacification of the central part of the IOL. The lens had to be explanted because of loss of visual acuity and glare sensation. Meanwhile, further opacifications occurred, also in other surgical centers using this IOL in Germany. The cases were reported to the German public authorities and the Food and Drug Administration, and our own investigations on the explanted lenses were begun.

Materials and Methods At present, 41 IOLs have been explanted from 39 patients. Two bilateral cases were observed. The mean time between cataract surgery and IOL explantation was 423 days, with a wide range of 55 to 683 days until explantation after cataract removal. Typically, a central gray-whitish, sometimes yellowish opacification of the IOL occurs (Fig 1). The opacification affects only the inner part of the lens, whereas a clear shell of constant thickness remains around the optical zone, as well as the haptics. Furthermore, a total reflection of light is obvious as a “second slit” in the slit-lamp image (Fig 2). Mostly, patient dissatisfaction consisted of blurred vision or even monocular double or triple images rather than a reduction in visual acuity. All explantations were scheduled because of patient dissatisfaction and not because of the visual acuity results assessed during the clinical examination. The mean age of the 18 male and 21 female patients was 71.1 years at the time of cataract surgery (standard deviation, 8.4 years). ISSN 0161-6420/01/$–see front matter PII S0161-6420(01)00778-3

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Figure 1. Central gray-white opacification of the explanted lens type SC60B-OUV (Medical Developmental Research, St. Petersburg, FL). A narrow, perfectly clear zone remains in the outer part of the optic as well as the haptics.

To identify a common property among the concerned patients, clinical data on their diseases, drugs, and serologic and blood analytic investigations were reviewed. Several of the patients neither had any disease nor used any drugs other than those prescribed by the ophthalmologists before and after surgery. No disease or medication of the other sometimes multimorbid patients may explain the alterations of the lenses. Rarely, in two of our cases, the complete lens body and also the haptic became opacified. In this study, only cases after explantation are mentioned. However, we also observed several early cases with only slightly opacified lenses. In these lenses, little dotlike spots of 10 ␮m diameter (estimated at the slit lamp) occurred in the center of the optic. All of the patients described in this article were operated on by either one (AF) of two surgeons. The phacoemulsification procedure in all patients followed an identical procedure. Preoperative medication: 500 mg Diamox orally (acetazolamide; Lederle, Wolfratshausen, Germany), Mydriatikum (tropicamide; Pharma Stulln, Stulln, Germany), Boroscopol (scopolamine; Winzer, Olching,

Figure 2. Slit-lamp photograph of an opacified intraocular lens (IOL). Central opacification is visible. Also, the slit-lamp light ray is reflected totally or scattered. Thus, the formation of four slits is observed, from right to left: corneal reflection, frontal lens shape, opacification, posterior lens shape, total reflection. This reflected light brings on the problem of multiple monocular images, one of the major reasons why patients request IOL explantation.

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Germany), Cyclopentolat 1% (cyclopentolate; Alcon, Freiburg, Germany), Voltaren ophtha (diclofenac; Ciba Vision GmbH, Großostheim, Germany), and Neosynephrine POS 5% (phenylephrine; Ursapharm, Saarbru¨ cken, Germany). Peribulbar block anesthesia with balloon, paracentesis, clear corneal incision, capsulorhexis under hyaluronic acid viscoelastic, hydrodissection with irrigation solution, phacoemulsification, irrigation and aspiration (I/A) with an I/A fluid containing 1 ml Suprarenin (adrenaline 1:1000; Hoechst, Frankfurt, Germany), cortical removal, implantation of an SC60B-OUV IOL folded with the Koch forceps (Hans Reinhard Koch, Heidelberg, Germany) under viscoelastics, I/A removal of viscoelastics, subconjunctival injection of Dexahexal 4 (dexamethasone 21 dihydrogen phosphate 4.37 mg/1 ml; Merck KgaA, Darmstadt, Germany) and Refobacin 10 mg (gentamicin; Merck KgaA). Postoperative ointments were used once: Floxal AS (ofloxacin; Dr Mann, Berlin, Germany), Glycocortison AS (hydrocortisone, glucose; Ciba Vision) or Spersacarpin 2% (pilocarpine; Ciba Vision). All patients were treated with Inflanegent (prednisolone acetate, gentamicine; PharmAllergan GmbH, Ettlingen, Germany) eyedrops for 3 days before surgery and 3 weeks after surgery. Also, either Ocuflur (flubiprofene; PharmAllergan) or Acular (ketorolac trometamol; PharmAllergan) eye drops were prescribed in the same period. All operations were performed in two different facilities. There were distinct differences between the facilities common to all patients operated in each theater: in the district hospital Siegen, all phacoemulsification procedures were performed using a Geuder Megatron phacomachine (Geuder, Heidelberg, Germany). Peribulbar block was performed using Carbostesin 0.5% (bupivacaine; Astra GmbH, Wedel, Germany), Ultracain 2% (articaine; Hoechst), and Hylase “Dessau” (hyaluronidase 150 IE, Pharma Dessau GmbH, Dessau, Germany). Irrigation solution used was Serag Ophthal BSS 500 ml (Serag Wiessner GmbH⫹Co KG, Naila, Germany) and Gentamicin ratiopharm 40SF (gentamicin 40 mg; Ratiopharm GmbH, Ulm, Germany). Viscoelastics used were Dispasan 0.5 ml (hyaluronic acid 10 mg/ml; Ciba Vision) or Viscorneal (sodium hyaluronate; Corneal, Paris, France). In the outpatient clinic facility Siegen, all procedures were performed with an OPSYS MMP (OMS Optical Microsystems, Andover, MA) phacomachine. Irrigation solutions used were Alcon BSS (Alcon) or Distra-SOL (NPBI International, Amsterdam, The Netherlands) with Refobacin 40 mg/500 ml (gentamicin; Merck). Viscoelastics used were Pe-Ha-Luron (sodium hyaluronate 1%; Peter Halfwassen, Unna, Germany), Microvisc (sodium hyaluronate 1%; Bohus Biotech AB, Stroemstrad, Sweden) or Healon (sodium hyaluronate 1%; Pharmacia & Upjohn, Erlangen, Germany). Block anesthetics used were Bucain 0.75% (bupivacaine; Curasan, Kleinostheim, Germany) and Xylonest 2% (prilocaine; Astra). Intravenous injections used were Dormicum (midazolam; Roche, Grenzach-Wyhlen, Germany) and Disoprivan 1% (propofole; Zeneca, Plankstadt, Germany). In case of an IOL explantation, the same drugs and equipment as described above were used. A scleral tunnel incision at the 12 o’clock position was prepared, followed by a temporal or nasal paracentesis. The anterior chamber was filled with one of the viscoelastic agents mentioned above. The IOL was mobilized from the capsular bag by careful injection of the viscoelastic agent into the space between the haptic and the capsule. If injection was not possible because of tight contact between the capsule and the haptic, a 150-␮m injection cannula was used for this maneuver, developed for viscocanalostomy by Stegmann et al.2 The lens was replaced then by a rigid PMMA IOL, inserted either into the sulcus or the capsular bag, if possible. The explanted lens was rinsed immediately in balanced salt solution and then was placed in a sterile vial filled with sterile balanced salt solution at room temperature.

Frohn et al 䡠 Late Opacification of Acrylic IOL sample loop, and measured at 280 nm for 25 minutes. No proteins could be found.

Laboratory Analysis: Spectrography

Figure 3. Photograph of the opacified intraocular lens material (light microscopy; original magnification, ⫻20). Dark, dotlike patterns are demonstrated in the opacified areas.

Results Evaluation using light microscopy (Fig 3) revealed a pattern of irregularly distributed round dots inside the lens material. Three lenses were stored in a sterile, dry vial after explantation. After 90 days, none of the IOLs became clear again.

Laboratory Chemical Analysis: Bleaching with H2O2 Six lenses were bleached in 3% H2O2 and Subtilisin A 0.4 mg (Allergan, Irvine, CA) for 5 hours. The bleaching process was performed under room temperature at 21° C. Macroscopically, no changes in opacification were observed after hydrogen dioxide treatment.

Laboratory Chemical Analysis: Search for Fatty Acids For the detection of fatty acids, three lenses were incubated in an autoclave. No fatty acids were detected.

Laboratory Chemical Analysis: Search for Proteins Two different methods were applied to detect proteins. To release every possible material precipitated in the polymer network, eight lenses were homogenized in an UltraTurrax homogenizer (Jancke and Kunkel, Staufen, Germany). By this machine, the polymer network is completely crushed. After that, the material was dissolved in sodium dodecyl sulfate sample buffer. The lens samples were separated by sodium dodecyl sulfate (polyacrylamide gel electrophoresis) on discontinuous 12% stab gels (Multigellong; Biometra, Go¨ ttingen, Germany). Staining with Coomassie-Blue and Sypro-Orange (Biorad, Mu¨ nchen, Germany) yielded no proteins. No staining could be detected in any of the lanes of the gels. Seven lenses were investigated with high-performance liquid chromatography (Model 2800; Biorad; with the BioDimension UV/ VIS monitor attached). In this process, the separation of agents is achieved by their molecular weight. A size exclusion column (BioSelect 250-5; BioRad) was used with an eluant of 0.4 M sodium phosphate buffer (pH 6.0). Five microliters of samples, which were prepared likewise in sodium dodecyl sulfate polyacrylamide gel electrophoresis were diluted in high-performance liquid chromatography buffer (sodium phosphate), injected in a 10-␮l

To identify the molecular origin of the opacification, six opacified lenses and one brand new, clear Medical Developmental Research SC60B-OUV lens were investigated with a Varian (Varian Inc., Palo Alto, CA) spectrometer, model Cary 50, instrument version 1.00, scan software 02.00(25), UV-Vis scan rate 24,000 nm/minute 5-nm data interval, UV-Vis average time 0.0125 seconds, dualbeam mode with baseline correction. All lenses showed a high absorption in the UV spectrum, ranging from 200 nm to more than 370 nm (Fig 4). Whereas the clear, unused IOL had a smooth absorption curve fitting with nearly 300% absorption of UV light, all of the explanted, opacified IOLs showed different UV spectra. All explanted IOLs had in common sharp absorption peaks within the UV spectrum (Fig 4A–C). Finally, we also found one cloudy IOL, that was still in the factory vial. This lens was originally sealed and had never been used in an operation. Nevertheless, the lens showed the typical opacification described here (Fig 5). Also, the fluid in the vial was contaminated by a large number of particles (Fig 5).

Discussion Although complications related to the foldable acrylic IOL itself are rare compared with the variety and number of implanted IOLs worldwide, a certain number of complications have been reported. Intraocular lens damage derived from the folding process are well documented.3–5 Surface alterations of unequivocal biological origin6,7 or on the IOL material itself8 –11 have been reported by several authors but cannot be correlated with the findings in our study, because the alterations afflict the inner body of the IOL itself. One group first assumed a common surgical factor9 in all concerned patients, but later dropped this idea,10 also as indicated by our observations. Alterations of the inner part of the IOL material are reported with respect to the AcrySof lens as fogging12 or glistenings. Glistenings are related to the formation of vacuoles inside the lens body after the temperature of the lens had risen beyond the glass transition temperature and water had entered the vacuoles.13–15 For this, glistenings are related to thermal effects inside the lens rather than to structural changes of the material itself. Thus, although glistenings also affect the inner parts of the lens material itself, they are not related to the mechanisms responsible for the lens alterations described here. Three lenses were stored in a dry vial after explantation. After 90 days, none of the lenses had become clear again. This fact excludes all speculations of water influence as in the AcrySof lens,13 because the glistenings disappeared after drying the lenses under laboratory conditions. Characteristics of the patients or the surgical procedure have to be shared in all cases to play a possible role in the origin of the phenomenon. Based on this hypothesis, the following factors can be excluded as a possible source for opacification, because they were not common in all cases: because they were otherwise healthy patients who were not using any systemic drug in the concerned group, systemic diseases and drug intake are excluded. Furthermore, the

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Figure 4. A, Spectral analysis of the material. The solid line indicates the spectrum of a clear (new, unused) Medical Developmental Research lens. The spectrum shows a sharp and regular filter effect for the ultraviolet (UV) spectrum. Whereas the optical density (OD) of 1 means 100% absorption, the readings of the absorption spectrum demonstrate an excessive amount of UV blocker (OD ⬎ 3). The dotted line indicates the spectrum of sample lens 1. The UV absorption has changed significantly. Sharp peaks of extremely high absorption are assessed. B, Spectral analysis of sample lens 2 also demonstrates changes in the UV spectrum; the peaks are located differently from those of sample lens 1. C, Spectral analysis of sample lens 3 also demonstrates changes in the UV spectrum; the peaks are located differently from those of sample lenses 1 and 2.

phacomachine (two in this study), a single surgeon (two in this study), the block anesthetics used, the viscoelastic agents, and the irrigation fluids do not qualify as a source. The only drugs used in all patients were the eye drops given before surgery and after surgery (Inflanegent, Ocuflur, or

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Acular), acetazolamide, ofloxacin ointment, subconjunctival injection of dexamethasone, and adrenaline in the I/A fluid. Protein adsorption to the IOL surface is a common problem and could explain differences in clinical behavior of

Frohn et al 䡠 Late Opacification of Acrylic IOL

Figure 5. This intraocular lens (IOL) is within an original, factory-sealed vial. The IOL already shows the typical signs of opacification. The transportation liquid is highly contaminated by particles.

different lens materials.16 Also, a hypothetical immunologic response of the eye would bring on proteins to the IOL in antigen–antibody complexes. By using the Ultra Turrax machine, the polymer network is crushed completely, thus releasing all materials probably precipitated inside of the three-dimensional matrix. Nevertheless, we could not detect any proteins buried in the lens material. With the exclusion of proteins as a source of the opacification, all patient- or biologically related sources for the phenomenon are unlikely except for minerals from the aqueous material. Mineral deposits on the IOL, as found in other lens types,17 go back to effects on or near the surface of the lens. Normally, these hydrogels have a very tight matrix, reducing the amount of minerals that can flow in and out. If there is damage to the matrix of the polymer, this could create microspaces for ions to gather. Our guess would be that if ion complexes form, they are most likely at or near the surface of the lens. But we do not believe there is evidence for minerals, so far, because the spectral changes indicate that an aging process of the UV blocker is the reason for the opacification. In addition, the opacification process starts in the center of the lens. The visible spectrum ranges from 400 to 760 nm, whereas the UV radiation starting at 200 nm and up to 400 nm is harmful to the retina. To protect the retina of the healthy human eye, UV-C radiation (200 –290 nm) is absorbed in the cornea, UV-B radiation (290 –320 nm) is absorbed by the lens capsule, and UV-A radiation (320 – 400 nm) is absorbed by the stroma of the lens.18 After cataract surgery, a significant part of the natural UV filter function is lost, which the IOL must replace. For this purpose, a UV-blocking agent is added routinely when manufacturing IOLs. From the spectral traces of the sample IOLs and the trace from a clean IOL, the level of UV blocking in the explanted lenses is much higher than would be needed for effectively blocking UV radiation (optical density ⬎ 3). A level of 1 absorption unit in the scale shown reflects 100% of the light absorbed. A higher concentration, although one can say is beneficial, is nonetheless excessive. This is an important finding that provides evidence that the

opacification has its origin in an accelerated aging process of the UV-blocking agent bound to the copolymer. The spectral analysis shows changes in the absorption profile taking place within the IOL. As mentioned, the amount of UV blocker used in this material is excessive. The opacification of the lenses can be attributed to an aging of the lens material after implantation. This aging could be a result of secondary reactions taking place within the polymer matrix that are initiated by changes in the UV absorber. The energy absorbed by the UV blocker, mostly from the UV-A region, could lead to a breakdown in some UV-blocking molecules, generating active radicals that in turn lead to side reactions within the matrix, with opacification of the material. Part of the polymerization process requires the elimination of residual initiator to avoid aging. Active species present in the matrix as a result of UV light could lead to other secondary reactions. Could the findings on the spectral analyses be secondary to the opacification itself? We assume that the changes in the material directly evoke the spectral changes. Any changes in the material should cause related changes in the spectrometric behavior, thus the spectrometric analysis gives a direct answer to the nature of the material changes. The absorption measurements in the UV spectral region showed up as distinct peaks, indicating the formation of new chemical products. Lenses presenting the same pattern of opacification have different spectral characteristics (Fig 4A–C). Assuming there are no other components beside PMMA and PHEMA, the spectral patterns indicate changes in the absorption pattern of the UV blocker, initiator, or both. Based on the component concentration, it appears to be primarily the UV blocker. The lenses examined were of various thickness, and some variation in the pattern is expected. Also, as mentioned above, various chemical reactions that form various resulting materials are to be expected. The spectral patterns depend on chemical properties like the length of side chains or the amount of double bindings. The aging process should be expected to have an erratic effect. Therefore, we expect variations in the spectra from different IOLs. The presence of a single opacified lens in a factorysealed vial gives additional evidence for the assumption that material-related problems are the origin of the opacification. Most likely is the aging process of the UV blocker. One may speculate that the original material sheet had been radiated by a certain amount of UV radiation before the manufacturing process, thus starting the aging process. The transportation medium also should be taken into consideration, because excessive contamination with particles was observed. The aging starts in the center of the lenses and grows to the borders. Two of our patients had complete opacifications of the whole lens material. This was not observed in all cases, because patients do not want to wait for this long period of time. They demand IOL explantation even if the complete material is not opacified. We expect that the complete lens would be opacified in all cases over time. Despite the outstanding number of explanted lenses in our series, more are expected. In our patients, we observed more IOLs developing opacification, but these patients for-

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Ophthalmology Volume 108, Number 11, November 2001 tunately have not experienced problems up to now. Only lenses that we explanted ourselves were included in this study. However, more cases of cloudy IOLs have come from Germany, France, and Italy. The only published report currently comes from the United Kingdom.19 These facts illustrate the common clinical impact of the opacification because the observed opacification is not an isolated case from a single facility. In 1949, Harold Ridley implanted the first IOL. Ridley chose PMMA as the best available material, because he noted in the injured eyes of pilots that the material was perfectly tolerated inside the eye. When Ridley implanted his first lens, there was only experience from World War II bomber pilots (max 4 years) who had glass implants from exploding cabin hoods inside their eyes. That means his experience with the biocompatibility was 4 years from the end of World War II. His risk was: what would happen after 5 or 10 years to his lenses. After the improvements to small-incision surgery facilitated the insertion of foldable lenses, a similar challenge occurred again: a variety of silicone foldable lenses were proposed. The experience with the silicone material has shown that 20% of the first silicone IOLs had to be exchanged between 3 and 4 years after surgery.20 It seems that every generation of surgeons has to face the same challenge again because new materials always pose the same questions regarding biocompatibility, endurance, and stability. The results from our laboratory investigations and clinical experiences underline the importance of controlled, prospective clinical studies on long-term safety issues in a field with an increasing number of new IOL materials.

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5. Pfister DR. Stress fractures after folding an acrylic intraocular lens. Am J Ophthalmol 1996;121:572– 4. 6. Shugar JK, Keeler S. Interpseudophakos intraocular lens surface opacification as a late complication of piggyback acrylic posterior chamber lens implantation. J Cataract Refract Surg 2000;26:448 –55. 7. Goarnisson S, Hennekes R. Medium term results of HEMA intraocular lenses (Hydroview). Bull Soc Belge Ophtalmol 1999;272:63– 8. 8. Hollick EJ, Spalton DJ, Ursell PG. Surface cytologic features on intraocular lenses: can increased biocompatibility have disadvantages? Arch Ophthalmol 1999;117:872– 8. 9. Jensen MK, Crandall AS, Mamalis N, Olson RJ. Crystallization on intraocular lens surfaces associated with the use of Healon GV. Arch Ophthalmol 1994;112:1037– 42. 10. Olson RJ. New cases of crystalline deposits on intraocular lenses not related to any specific viscoelastic [letter]. Arch Ophthalmol 1995;113:1229. 11. Amon M, Menapace R. In vivo observation of surface precipitates of 200 consecutive hydrogel intraocular lenses. Ophthalmologica 1992;204:13– 8. 12. McKibbin M, Seemongal-Dass RR, Atkinson PL. Transient fogging of acrylic (AcrySof) intraocular lenses [letter]. Eye 1999;13:672–3. 13. Omar O, Pirayesh A, Mamalis N, Olson RJ. In vitro analysis of AcrySof intraocular lens glistenings in AcryPak and Wagon Wheel packaging. J Cataract Refract Surg 1998;24:107–13. 14. Dogru M, Tetsumoto K, Tagami Y, et al. Optical and atomic force microscopy of an explanted AcrySof intraocular lens with glistenings. J Cataract Refract Surg 2000;26:571–5. 15. Peetermans E, Hennekes R. Long-term results of Wagon Wheel packed acrylic intra-ocular lenses (AcrySof). Bull Soc Belge Ophtalmol 1999;271:45– 8. 16. Johnston RL, Spalton DJ, Hussain A, Marshall J. In vitro protein adsorption to 2 intraocular lens materials. J Cataract Refract Surg 1999;25:1109 –15. 17. Apple DJ, Werner L, Escobar-Gomez M, Pandey SK. Deposits on the optical surfaces of Hydroview intraocular lenses [letter]. J Cataract Refract Surg 2000;26:796 –7. 18. Abadi RV, Davies IP, Papas E. The spectral transmittance of hydrogel contact lens filters. Opthalmic Physiol Opt 1989;9: 360 –7. 19. Chang BY, Davey KG, Gupta M, Hutchinson C. Late clouding of an acrylic intraocular lens following routine phacoemulsification [letter]. Eye 1999;13:807– 8. 20. Aron-Rosa D. Nouveaux biomate´ riaux et chirurgie de lacataracte. Bull Acad Natl Med 1995;179:557– 66; discussion 566 –7.