- Email: [email protected]
Opacification of Array SA40N silicone multifocal intraocular lens
J CATARACT REFRACT SURG - VOL 33, FEBRUARY 2007
Opacification of Array SA40N silicone multifocal intraocular lens Mostafa Elgohary, MSc MD, FRCSI, FRCSEd, MRCOphth, Asad Zaheer, FRCSEd, Liliana Werner, MD, PhD, Alex Ionides, MD, FRCS, FRCOphth, James Sheldrick, FRCS, FRCOphth, Nisar Ahmed, FRCSI, FRCS, FRCOphth
We report opacification of 2 multifocal intraocular lenses (IOLs). Patients with these IOLs may be more likely to require IOL explantation than those with monofocal IOLs. J Cataract Refract Surg 2007; 33:342–347 Q 2007 ASCRS and ESCRS
Opacification of intraocular lens (IOL) optics has been described with all types of IOL material including poly(methyl methacrylate),1 hydrophilic,2,3 hydrophobic acrylic,4,5 and silicone.6–16 Silicone IOL opacification has been described in association with first-6–9 and second-generation IOLs,10–16 as well as with different IOL designs including plate-haptic11 and 3-piece,10,12,16 and has been found to be one cause of silicone IOL explantation, constituting 2.5% of cases.17 The Array SA40N IOL (Advanced Medical Optics) is a second-generation silicone multifocal IOL. The IOL optic has a refractive index of 1.46 and 5 concentric zones that divide the incident light between near, intermediate, and distance foci and therefore enable focusing at different distances. The IOL is known to reduce contrast sensitivity, although this has been shown to have a limited clinical
Accepted for publication September 17, 2006. From the Essex County Hospital (Elgohary, Zaheer, Sheldrick, Ahmed), Colchester, and Moorfields Eye Hospital (Ionides), London, United Kingdom; and the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, and Berlin Eye Research Institute (Werner), Berlin, Germany. No author has a financial or proprietary interest in any material or method mentioned. Supported in part by the Research to Prevent Blindness Olga Keith Wiess Scholar Award (Werner). Presented as an e-poster at the XXIVth Congress of the European Society of Cataract and Refractive Surgeons, London, England, September 2006. David M. Andrenyak, Center for Human Toxicology, University of Utah, assisted with the laboratory analysis. Corresponding author: Mostafa Elgohary, Essex County Hospital, Lexden Road, Colchester CO3 3NB, United Kingdom. E-mail: [email protected]. Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
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effect.18–21 In this report, we describe 2 patients who developed opacification of Array SA40N IOLs shortly after uneventful phacoemulsification. We discuss the possible mechanism and potential clinical implications of opacification of this IOL. CASE REPORTS Case 1 A 59-year-old woman presented with blurred vision 1 week after phacoemulsification and IOL implantation of a multifocal IOL (Array SA40N, serial number 1027080106) in the left eye. On examination, the Snellen visual acuity was 6/9 in the right eye and 6/6 in the left eye. Gray–white to faint brown discoloration of the optic was visible in the left eye (Figure 1, top), and the right eye had mild nuclear cataract. The anterior segment and fundus were otherwise unremarkable, and the intraocular pressure (IOP) was 12 mm Hg in both eyes. The patient had no history of medical or ocular diseases and was not on any medications. She worked in the porcelain industry and had worked on a kiln but avoided that in the postoperative period. Cataract surgery had been performed under local sub-Tenon’s anesthesia (lignocaine 2%, B Braun) after the pupil was dilated using nonpreserved cyclopentolate 1% and phenylepherine 2.5% (Chauvin). A hydroxypropyl methylcellulose ophthalmic viscosurgical device (OVD) (Acri.Viscose, Acri-Tec) was used to assist capsulorhexis and implantation of the IOL. The irrigating solution was balanced salt solution (BSS, Alcon Laboratories) with 1:200 000 adrenaline. At the conclusion of the procedure, cefuroxime (Zinacef, Glaxo Wellcome) 125 mg was injected in the subconjunctival space. Postoperatively, dexamethasone 0.1%– neomycin sulfate 0.35%–polymyxin B sulfate (Maxitrol, Alcon) 6000 units/g was prescribed 4 times a day for 2 weeks and then 2 times a day for 2 weeks. Six weeks later, although the visual acuity remained 6/6, the patient complained of persistent blurring of vision in the left eye. The logMAR 10% low-contrast acuity (at 3 meters) was 0.2 and 1 in the right eye and left eye, respectively. Three months later, explantation of the IOL was carried out and a hydrophobic acrylic IOL (AcrySof, Alcon) implanted. Subjectively, the patient 0886-3350/07/$-see front matter doi:10.1016/j.jcrs.2006.09.034
CASE REPORTS: OPACIFICATION OF ARRAY MULTIFOCAL IOL
Figure 1. Slitlamp photographs of the 2 cases. Top: Case 1 (left eye), showing gray– white to faint brown discoloration. Bottom: Case 2 (right eye), showing gray brown discoloration of the IOL optic.
appreciated increased clarity of vision; the visual acuity improved to 6/5 and logMAR low-contrast acuity increased to 0.1.
and were used to identify the corresponding chemical from library matches. Case 2
Examination of the Explanted IOL The explanted IOL was sent for microscopic and laboratory analysis in a vial containing BSS. Gross examination showed white discoloration of the IOL in the hydrated state, which gradually cleared from the periphery toward the center after the IOL was left outside the container to dry (Figure 2). Light microscopic analysis did not reveal deposits on the external surfaces or within the substance of the IOL. The IOL was divided and one half was sent to the manufacturer (AMO) for laboratory analysis and the other half for analysis at the Center for Human Toxicology, University of Utah. The IOL was incubated at 50 C, and the emitted vapors were trapped with solid-phase microextraction (SPME) and analyzed using gas chromatography mass spectroscopy (GCMS). This technique serves to identify exogenous molecules in the IOL optic that might have been absorbed or that are normally filtered and removed. The transit fluid sample extracts of the 2 halves were analyzed by GCMS. The results of the analysis are detailed in Tables 1 and 2. The numbers in Table 2 correlate with the retention time of each of the extracted molecules and their rendered chromatographic peaks. These were compared with those of a water sample
A 79-year-old woman had phacoemulsification in the right eye. After surgery, she developed striate keratitis and was maintained on topical steroids for 4 weeks. Eight weeks postoperatively, the corneal edema resolved but the IOL was brown (Figure 1, bottom) and the patient complained of blurring of vision. Visual acuity was 6/12 in both eyes, improving with the pinhole to 6/9 in the right eye and 6/6 in the left eye. The logMAR low-contrast acuity was 0.8 and 0.2 in the right eye and left eye, respectively. Anterior segment and fundus examinations were otherwise unremarkable, and IOP was 16 mm Hg. There was no relevant ocular or medical history, and the patient was not on any medications. Three years earlier, she had had uneventful phacoemulsification and implantation of an Array SA40N silicone multifocal IOL (Advanced Medical Optics, Inc) in the left eye and an uneventful postoperative course; the IOL in that eye was clear. Operative notes revealed that intraoperative and postoperative medications as well as the surgical technique were similar in both eyes. Sodium hyaluronate OVD was used to facilitate the capsulorhexis and implantation of the IOL; the irrigating solution was the same as in Case 1. A multifocal IOL (Array SA40N, serial number 1774410202) was implanted using an IOL folder and
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Figure 2. The AMO Array IOL explanted from Case 1 after removal from the solution. Top: Gross photographs show the graywhite discoloration gradually clearing from the periphery toward the center after removal from the BSS solution. Bottom: Light microscopy view using the Nikon D1X camera with an ED28-70 lens (original magnification 40).
forceps. Subconjunctival injections of Zinacef (Glaxo Wellcome), 125 mg, and betamethasone sodium phosphate 0.1% (Betnesol, Medeva) were performed at the end of surgery. Postoperatively, prednisolone acetate 1% (Pred Forte, Allergan) and chloramphenicol 0.1% were prescribed 4 times a day for 2 weeks and then 2 times a day for 2 weeks. The patient declined to have the opacified IOL explanted and replaced. DISCUSSION
Several mechanisms have been proposed to explain the possible causes of silicone IOL opacification. Some manufacturers (Iolab and Allergan Medical Optics) suggest the opacification might be related to the presence of low molecular weight silicone fractions that were not crosslinked during the curing process9 or to large polymer impurities due to inadequate filtering that led to lens hydration by allowing water vapor to diffuse into the silicone material.22 Kershner23 suggests a possible interaction between the silicone material and some intraoperative or postoperative medications. In our patients, lens hydration was the most likely mechanism. The 2 IOLs appeared gray–white to brown clinically (Figure 1); the explanted IOL resumed clarity on removal from the BSS and had no deposits on the surfaces or within the IOL (Figure 2). Also, the opacification was noted within 2 to 8 weeks of surgery, although it is possible that the opacification had developed soon after implantation or even intraoperatively. Although we could not examine the IOL in the second patient, the similarity
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in clinical features and time of onset suggest a similar mechanism of opacification. The above features are similar to those described in previous reports of IOL opacification attributed to lens hydration. Hilgert et al.12 describe 4 patients who developed nonprogressive gray–white to brown opacification of an SI40NB IOL (AMO) on the first postoperative day. Similar to our explanted IOL, the 3 explanted lenses in that report did not have deposits on the surfaces or within and the opacification existed in the hydrated state only. Tanaka et al.10 report opacification of another SI40NB IOL on the first postoperative day. Microscopic examination showed spheroid deposits on the surface of the central region but not within the IOL. The SI40NB IOLs are similar to the Array SA40N in Table 1. Results of the laboratory analysis of one half of the IOL optic by AMO.
Method of Analysis Vapors by SPME–GCMS
Extracts by GCMS
Compounds Detected Di-t-butylphenol BHT-aldehyde Triisopropylbenzene Trace aliphatic hydrocarbons Trace aromatic hydrocarbons Dibutylphthalate Lidocaine Cholesterol Cholestenone
GCMS Z gas chromatography mass spectroscopy; SPME Z solid-phase microextraction
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Table 2. Results of the analysis of one half of the IOL optic by the Center for Human Toxicology.
Sample
Peak
Retention Time
Blank water: Base extraction BB-1 3.651 BB-2 5.870 BB-3 7.249 BB-4 7.761 BB-5 8.577 BB-6 8.988 BB-7 12.188 Liquid that suspended the IOL: Base extraction LB-1 3.645 LB-2 5.783 LB-3 5.871 LB-4 7.244 LB-5 8.578 LB-6 8.666 LB-7 9.001 LB-8 11.234 LB-9 12.182 LB-10 13.328 LB-11 12.422 LB-12 12.536 Blank water: Acid extraction BA-1 8.994 BA-2 10.809 BA-3 11.220 BA-4 11.523 BA-5 12.181 Ba-6 5.870 Liquid that suspended the IOL: Acid extraction LA-1 3.656 LA-2 4.712 LA-3 4.863 LA-4 7.241 LA-5 7.279 LA-6 8.575 LA-7 8.657 LA-8 8.746 LA-9 8.993 LA-10 11.231 LA-11 11.364 LA-12 11.478 LA-13 12.180 Basic drug standard: 800 ng/mL: Base extraction STD_LIDO 8.666
design and in optic and haptic materials, and the authors describe features of opacification and pathological changes similar to those in our IOLs. Tanaka et al.10 suggest that along with the chemical composition of the optic, hydration of the IOL could have played a role in producing the opacification. Although the 2 IOLs in our cases came from different production lots, the opacification seems more likely to be related to a manufacturing or processing anomaly that
Major Ion Fragments
Possible Chemical Identification
119, 154, 91 191, 206 58, 241 266, 165, 230 58, 108 149, 223 149, 279
p-ethyl benzyl chloride Phenol, 2,4-bis(1,1-dimethylethyl)N,N-Dimethyltetradecanamine Phenol, pentachloro No good library match Dibutyl phthalate Bis(2-ethylhexyl) phthalate
119, 154, 91 58, 213 191, 206 58, 241 58, 269 86, 234 149, 223 59, 518, 490 149, 167, 279 253, 370 239, 356, 584 253, 370
p-ethylbenzyl chloride 1-dodecanamine, N,N-dimethylPhenol, 2,4-bis(1,1-dimethylethyl)N,N-dimethyltetradecanamine Cetrimonium bromde Lidocaine Dibutyl phthalate No good library match Bis(2-ethylhexyl)phthalate No good library match No good library match No good library match
149, 223 347, 177, 489 59, 188, 461, 532 515, 160, 292 149, 279 191, 206, 115
Dibutyl phthalate No good library match No good library match No good library match Bis(2-ethylhexyl)phthalate Phenol, 2, 4-bis(1,1-dimethylethyl)-
119, 154, 91 43, 71, 98 71, 89, 143, 173 58, 241 99, 81, 592 58, 269, 114 86, 120 205, 383, 597 149, 223 59, 126, 526 253, 496, 589 239, 439, 526 149, 167, 279
p-ethylbenzyl chloride No good library match No good library match N,N-dimethyltetradecanamide No good library match Centrimonium Bromide Lidocaine No good library match Dibutyl phthalate No good library match No good library match No good library match Bis(2-ethylhexyl)phthalate
86, 234
Lidocaine
rendered the IOL material hydrophilic and readily permeable to water molecules than to surgery or perioperative medications. The 2 patients were operated on by different surgeons (J.S. and N.A.) on different surgical lists using 2 OVD materials. Moreover, 1 patient had a similar procedure in the other eye but the IOL remained clear. Notably, a chromatographic peak for lidocaine was detected in the extract prepared from the lens suspension
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liquid of the explanted IOL but not in the blank water extract, which indicates that it was not an analytical artifact. Although this does not necessarily suggest a causal relationship to the opacification, it concurs with the suggestion by Kershner.23 Opacification related to deposits from silicone oil,24 an ophthalmic ointment15 as well as systemic medications such as amiodarone25 and rifabutin26 have been described. Most published cases describe clinically insignificant opacification that did not require explantation, and several factors seem to affect the patient’s need for explantation, including the magnitude of the opacity, the patient’s lifestyle, and perhaps the preoperative visual acuity. Our cases suggest that the optical design of the IOL through its effect on visual functions other than visual acuity may be an important determinant of whether the patient will need explantation; 1 of our patients required explantation despite relatively good visual acuity. Perhaps the reduction in contrast sensitivity, a function that is already compromised because of the optical design of the multifocal IOL, is probably the main incentive for explantation by patients with these IOLs. Although it has a potentially severe effect on vision, opacification of silicone IOLs is a rare complication. Recent estimates suggest an incidence of approximately 3 in 1 000 000 for AMO silicone IOLs (Tanaka et al.10) and 1 in 10 000 for the SA40N (personal communication). Clinically significant opacification remains more rare. No case of explantation of 3-piece silicone IOLs, including the SA40N, has been reported in the most recent survey by the American Society of Cataract and Refractive Surgery and the European Society of Cataract and Refractive Surgeons (N. Mamalis, et al. ‘‘Survey of Foldable IOLs Requiring Explantation or Secondary Intervention: 2005 Update,’’ presented at the XXIVth Congress of the European Society of Cataract and Refractive Surgeons, London, United Kingdom, September 2006). In conclusion, we have reported the opacification of 2 Array SA40N silicone multifocal IOLs, a phenomenon that has been seen in other silicone IOLs and appears to be related to an aberrant increase in the hydrophilicity of the silicone material of the optic. The effect of IOL opacification on visual acuity and contrast sensitivity functions may lead to more likelihood of patients with multifocal IOLs requiring explantation. Although the opacification is rare, further investigations are needed to identify the exact cause and reduce or even prevent its occurrence and thereby improve the overall compatibility and outcome with these IOLs.
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REFERENCES 1. Apple DJ, Peng Q, Arthur SN, et al. Snowflake degeneration of polymethylmethacrylate posterior chamber intraocular lens optic material; a newly described clinical condition caused by unexpected late
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opacification of polymethyl methacrylate. Ophthalmology 2002; 109: 1666–1675 Werner L, Apple DJ, Kaskaloglu M, Pandey SK. Dense opacification of the optical component of a hydrophilic acrylic intraocular lens; a clinicopathological analysis of 9 explanted lenses. J Cataract Refract Surg 2001; 27:1485–1492 Pandey SK, Werner L, Apple DJ, Gravel J-P. Calcium precipitation on the optical surfaces of a foldable intraocular lens: a clinicopathological correlation. Arch Ophthalmol 2002; 120:391–393 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; 24:107–113 Dhaliwal DK, Mamalis N, Olson RJ, et al. Visual significance of glistenings seen in the AcrySof intraocular lens. J Cataract Refract Surg 1996; 22:452–457 Milauskas AT. Silicone intraocular lens implant discoloration in humans [letter]. Arch Ophthalmol 1991; 109:913 Nimoy M. Silicone intraocular lens implant discoloration in humans [letter]. Arch Ophthalmol 1991; 109:1057 Watt RH. Discoloration of a silicone intraocular lens 6 weeks after surgery [letter and reply by AT Milauskas]. Arch Ophthalmol 1991; 109:1494–1495 Koch DD, Heit LE. Discoloration of silicone intraocular lenses [letter]. Arch Ophthalmol 1992; 110:319–320 Tanaka T, Saika S, Hashizume N, Ohnishi Y. Brown haze in an Allergan SI-40NB silicone intraocular lens. J Cataract Refract Surg 2004; 30: 250–252 Foot L, Werner L, Gills JP, et al. Surface calcification of silicone plate intraocular lenses in patients with asteroid hyalosis. Am J Ophthalmol 2004; 137:979–987 Hilgert CR, Hilgert A, Ho¨fling-Lima AL, et al. Early opacification of SI-40NB silicone intraocular lenses. J Cataract Refract Surg 2004; 30:2225–2229 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 Werner L, Kollarits CR, Mamalis N, Olson RJ. Surface calcification of a 3-piece silicone intraocular lens in a patient with asteroid hyalosis; a clinicopathologic case report. Ophthalmology 2005; 112:447–452 Chew JJL, Werner L, Mackman G, Mamalis N. Late opacification of a silicone intraocular lens caused by ophthalmic ointment. J Cataract Refract Surg 2006; 32:341–346 Werner L, Dornelles F, Hilgert CR, et al. Early opacification of silicone intraocular lenses: laboratory analyses of 6 explants. J Cataract Refract Surg 2006; 32:499–509 Mamalis N, Davis B, Nilson CD, et al. Complications of foldable intraocular lenses requiring explantation or secondary interventiond2003 survey update. J Cataract Refract Surg 2004; 30:2209–2218 Steinert RF, Aker BL, Trentacost DJ, et al. A prospective comparative study of the AMO ARRAY zonal-progressive multifocal silicone intraocular lens and a monofocal intraocular lens. Ophthalmology 1999; 106:1243–1255 Schmitz S, Dick HB, Krummenauer F, et al. Contrast sensitivity and glare disability by halogen light after monofocal and multifocal lens implantation. Br J Ophthalmol 2000; 84:1109–1112 Monte´s-Mico´ R, Espan˜a E, Bueno I, et al. Visual performance with multifocal intraocular lenses; mesopic contrast sensitivity under distance and near conditions. Ophthalmology 2004; 111:85–96 Elgohary MA, Beckingsale AB. Effect of illumination on visual function after multifocal and monofocal intraocular lens implantation. Eye 2006; 20:144–149 Ziemba SL. In reply to Milauskas AT. Silicone intraocular lens implant discoloration in humans [letter]. Arch Ophthalmol 1991; 109:914–915
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23. Kershner RM. In reply to Milauskas AT. Silicone intraocular lens implant discoloration in humans [letter]. Arch Ophthalmol 1991; 109:913–914 24. Apple DJ, Federman JL, Krolicki TJ, et al. Irreversible silicone oil adhesion to silicone intraocular lenses; a clinicopathological analysis. Ophthalmology 1996; 103:1555–1561; discussion by TM Aaberg Sr, 1561–1562
25. Katai N, Yokoyama R, Yoshimura N. Progressive brown discoloration of silicone intraocular lenses after vitrectomy in a patient on amiodarone. J Cataract Refract Surg 1999; 25:451–452 26. Jones DF, Irwin AE. Discoloration of intraocular lens subsequent to rifabutin use. Arch Ophthalmol 2002; 120:1211–1212
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Opacification of Array SA40N silicone multifocal intraocular lens Mostafa Elgohary, MSc MD, FRCSI, FRCSEd, MRCOphth, Asad Zaheer, FRCSEd, Liliana Werner, MD, PhD, Alex Ionides, MD, FRCS, FRCOphth, James Sheldrick, FRCS, FRCOphth, Nisar Ahmed, FRCSI, FRCS, FRCOphth
We report opacification of 2 multifocal intraocular lenses (IOLs). Patients with these IOLs may be more likely to require IOL explantation than those with monofocal IOLs. J Cataract Refract Surg 2007; 33:342–347 Q 2007 ASCRS and ESCRS
Opacification of intraocular lens (IOL) optics has been described with all types of IOL material including poly(methyl methacrylate),1 hydrophilic,2,3 hydrophobic acrylic,4,5 and silicone.6–16 Silicone IOL opacification has been described in association with first-6–9 and second-generation IOLs,10–16 as well as with different IOL designs including plate-haptic11 and 3-piece,10,12,16 and has been found to be one cause of silicone IOL explantation, constituting 2.5% of cases.17 The Array SA40N IOL (Advanced Medical Optics) is a second-generation silicone multifocal IOL. The IOL optic has a refractive index of 1.46 and 5 concentric zones that divide the incident light between near, intermediate, and distance foci and therefore enable focusing at different distances. The IOL is known to reduce contrast sensitivity, although this has been shown to have a limited clinical
Accepted for publication September 17, 2006. From the Essex County Hospital (Elgohary, Zaheer, Sheldrick, Ahmed), Colchester, and Moorfields Eye Hospital (Ionides), London, United Kingdom; and the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA, and Berlin Eye Research Institute (Werner), Berlin, Germany. No author has a financial or proprietary interest in any material or method mentioned. Supported in part by the Research to Prevent Blindness Olga Keith Wiess Scholar Award (Werner). Presented as an e-poster at the XXIVth Congress of the European Society of Cataract and Refractive Surgeons, London, England, September 2006. David M. Andrenyak, Center for Human Toxicology, University of Utah, assisted with the laboratory analysis. Corresponding author: Mostafa Elgohary, Essex County Hospital, Lexden Road, Colchester CO3 3NB, United Kingdom. E-mail: [email protected]. Q 2007 ASCRS and ESCRS Published by Elsevier Inc.
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effect.18–21 In this report, we describe 2 patients who developed opacification of Array SA40N IOLs shortly after uneventful phacoemulsification. We discuss the possible mechanism and potential clinical implications of opacification of this IOL. CASE REPORTS Case 1 A 59-year-old woman presented with blurred vision 1 week after phacoemulsification and IOL implantation of a multifocal IOL (Array SA40N, serial number 1027080106) in the left eye. On examination, the Snellen visual acuity was 6/9 in the right eye and 6/6 in the left eye. Gray–white to faint brown discoloration of the optic was visible in the left eye (Figure 1, top), and the right eye had mild nuclear cataract. The anterior segment and fundus were otherwise unremarkable, and the intraocular pressure (IOP) was 12 mm Hg in both eyes. The patient had no history of medical or ocular diseases and was not on any medications. She worked in the porcelain industry and had worked on a kiln but avoided that in the postoperative period. Cataract surgery had been performed under local sub-Tenon’s anesthesia (lignocaine 2%, B Braun) after the pupil was dilated using nonpreserved cyclopentolate 1% and phenylepherine 2.5% (Chauvin). A hydroxypropyl methylcellulose ophthalmic viscosurgical device (OVD) (Acri.Viscose, Acri-Tec) was used to assist capsulorhexis and implantation of the IOL. The irrigating solution was balanced salt solution (BSS, Alcon Laboratories) with 1:200 000 adrenaline. At the conclusion of the procedure, cefuroxime (Zinacef, Glaxo Wellcome) 125 mg was injected in the subconjunctival space. Postoperatively, dexamethasone 0.1%– neomycin sulfate 0.35%–polymyxin B sulfate (Maxitrol, Alcon) 6000 units/g was prescribed 4 times a day for 2 weeks and then 2 times a day for 2 weeks. Six weeks later, although the visual acuity remained 6/6, the patient complained of persistent blurring of vision in the left eye. The logMAR 10% low-contrast acuity (at 3 meters) was 0.2 and 1 in the right eye and left eye, respectively. Three months later, explantation of the IOL was carried out and a hydrophobic acrylic IOL (AcrySof, Alcon) implanted. Subjectively, the patient 0886-3350/07/$-see front matter doi:10.1016/j.jcrs.2006.09.034
CASE REPORTS: OPACIFICATION OF ARRAY MULTIFOCAL IOL
Figure 1. Slitlamp photographs of the 2 cases. Top: Case 1 (left eye), showing gray– white to faint brown discoloration. Bottom: Case 2 (right eye), showing gray brown discoloration of the IOL optic.
appreciated increased clarity of vision; the visual acuity improved to 6/5 and logMAR low-contrast acuity increased to 0.1.
and were used to identify the corresponding chemical from library matches. Case 2
Examination of the Explanted IOL The explanted IOL was sent for microscopic and laboratory analysis in a vial containing BSS. Gross examination showed white discoloration of the IOL in the hydrated state, which gradually cleared from the periphery toward the center after the IOL was left outside the container to dry (Figure 2). Light microscopic analysis did not reveal deposits on the external surfaces or within the substance of the IOL. The IOL was divided and one half was sent to the manufacturer (AMO) for laboratory analysis and the other half for analysis at the Center for Human Toxicology, University of Utah. The IOL was incubated at 50 C, and the emitted vapors were trapped with solid-phase microextraction (SPME) and analyzed using gas chromatography mass spectroscopy (GCMS). This technique serves to identify exogenous molecules in the IOL optic that might have been absorbed or that are normally filtered and removed. The transit fluid sample extracts of the 2 halves were analyzed by GCMS. The results of the analysis are detailed in Tables 1 and 2. The numbers in Table 2 correlate with the retention time of each of the extracted molecules and their rendered chromatographic peaks. These were compared with those of a water sample
A 79-year-old woman had phacoemulsification in the right eye. After surgery, she developed striate keratitis and was maintained on topical steroids for 4 weeks. Eight weeks postoperatively, the corneal edema resolved but the IOL was brown (Figure 1, bottom) and the patient complained of blurring of vision. Visual acuity was 6/12 in both eyes, improving with the pinhole to 6/9 in the right eye and 6/6 in the left eye. The logMAR low-contrast acuity was 0.8 and 0.2 in the right eye and left eye, respectively. Anterior segment and fundus examinations were otherwise unremarkable, and IOP was 16 mm Hg. There was no relevant ocular or medical history, and the patient was not on any medications. Three years earlier, she had had uneventful phacoemulsification and implantation of an Array SA40N silicone multifocal IOL (Advanced Medical Optics, Inc) in the left eye and an uneventful postoperative course; the IOL in that eye was clear. Operative notes revealed that intraoperative and postoperative medications as well as the surgical technique were similar in both eyes. Sodium hyaluronate OVD was used to facilitate the capsulorhexis and implantation of the IOL; the irrigating solution was the same as in Case 1. A multifocal IOL (Array SA40N, serial number 1774410202) was implanted using an IOL folder and
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Figure 2. The AMO Array IOL explanted from Case 1 after removal from the solution. Top: Gross photographs show the graywhite discoloration gradually clearing from the periphery toward the center after removal from the BSS solution. Bottom: Light microscopy view using the Nikon D1X camera with an ED28-70 lens (original magnification 40).
forceps. Subconjunctival injections of Zinacef (Glaxo Wellcome), 125 mg, and betamethasone sodium phosphate 0.1% (Betnesol, Medeva) were performed at the end of surgery. Postoperatively, prednisolone acetate 1% (Pred Forte, Allergan) and chloramphenicol 0.1% were prescribed 4 times a day for 2 weeks and then 2 times a day for 2 weeks. The patient declined to have the opacified IOL explanted and replaced. DISCUSSION
Several mechanisms have been proposed to explain the possible causes of silicone IOL opacification. Some manufacturers (Iolab and Allergan Medical Optics) suggest the opacification might be related to the presence of low molecular weight silicone fractions that were not crosslinked during the curing process9 or to large polymer impurities due to inadequate filtering that led to lens hydration by allowing water vapor to diffuse into the silicone material.22 Kershner23 suggests a possible interaction between the silicone material and some intraoperative or postoperative medications. In our patients, lens hydration was the most likely mechanism. The 2 IOLs appeared gray–white to brown clinically (Figure 1); the explanted IOL resumed clarity on removal from the BSS and had no deposits on the surfaces or within the IOL (Figure 2). Also, the opacification was noted within 2 to 8 weeks of surgery, although it is possible that the opacification had developed soon after implantation or even intraoperatively. Although we could not examine the IOL in the second patient, the similarity
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in clinical features and time of onset suggest a similar mechanism of opacification. The above features are similar to those described in previous reports of IOL opacification attributed to lens hydration. Hilgert et al.12 describe 4 patients who developed nonprogressive gray–white to brown opacification of an SI40NB IOL (AMO) on the first postoperative day. Similar to our explanted IOL, the 3 explanted lenses in that report did not have deposits on the surfaces or within and the opacification existed in the hydrated state only. Tanaka et al.10 report opacification of another SI40NB IOL on the first postoperative day. Microscopic examination showed spheroid deposits on the surface of the central region but not within the IOL. The SI40NB IOLs are similar to the Array SA40N in Table 1. Results of the laboratory analysis of one half of the IOL optic by AMO.
Method of Analysis Vapors by SPME–GCMS
Extracts by GCMS
Compounds Detected Di-t-butylphenol BHT-aldehyde Triisopropylbenzene Trace aliphatic hydrocarbons Trace aromatic hydrocarbons Dibutylphthalate Lidocaine Cholesterol Cholestenone
GCMS Z gas chromatography mass spectroscopy; SPME Z solid-phase microextraction
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Table 2. Results of the analysis of one half of the IOL optic by the Center for Human Toxicology.
Sample
Peak
Retention Time
Blank water: Base extraction BB-1 3.651 BB-2 5.870 BB-3 7.249 BB-4 7.761 BB-5 8.577 BB-6 8.988 BB-7 12.188 Liquid that suspended the IOL: Base extraction LB-1 3.645 LB-2 5.783 LB-3 5.871 LB-4 7.244 LB-5 8.578 LB-6 8.666 LB-7 9.001 LB-8 11.234 LB-9 12.182 LB-10 13.328 LB-11 12.422 LB-12 12.536 Blank water: Acid extraction BA-1 8.994 BA-2 10.809 BA-3 11.220 BA-4 11.523 BA-5 12.181 Ba-6 5.870 Liquid that suspended the IOL: Acid extraction LA-1 3.656 LA-2 4.712 LA-3 4.863 LA-4 7.241 LA-5 7.279 LA-6 8.575 LA-7 8.657 LA-8 8.746 LA-9 8.993 LA-10 11.231 LA-11 11.364 LA-12 11.478 LA-13 12.180 Basic drug standard: 800 ng/mL: Base extraction STD_LIDO 8.666
design and in optic and haptic materials, and the authors describe features of opacification and pathological changes similar to those in our IOLs. Tanaka et al.10 suggest that along with the chemical composition of the optic, hydration of the IOL could have played a role in producing the opacification. Although the 2 IOLs in our cases came from different production lots, the opacification seems more likely to be related to a manufacturing or processing anomaly that
Major Ion Fragments
Possible Chemical Identification
119, 154, 91 191, 206 58, 241 266, 165, 230 58, 108 149, 223 149, 279
p-ethyl benzyl chloride Phenol, 2,4-bis(1,1-dimethylethyl)N,N-Dimethyltetradecanamine Phenol, pentachloro No good library match Dibutyl phthalate Bis(2-ethylhexyl) phthalate
119, 154, 91 58, 213 191, 206 58, 241 58, 269 86, 234 149, 223 59, 518, 490 149, 167, 279 253, 370 239, 356, 584 253, 370
p-ethylbenzyl chloride 1-dodecanamine, N,N-dimethylPhenol, 2,4-bis(1,1-dimethylethyl)N,N-dimethyltetradecanamine Cetrimonium bromde Lidocaine Dibutyl phthalate No good library match Bis(2-ethylhexyl)phthalate No good library match No good library match No good library match
149, 223 347, 177, 489 59, 188, 461, 532 515, 160, 292 149, 279 191, 206, 115
Dibutyl phthalate No good library match No good library match No good library match Bis(2-ethylhexyl)phthalate Phenol, 2, 4-bis(1,1-dimethylethyl)-
119, 154, 91 43, 71, 98 71, 89, 143, 173 58, 241 99, 81, 592 58, 269, 114 86, 120 205, 383, 597 149, 223 59, 126, 526 253, 496, 589 239, 439, 526 149, 167, 279
p-ethylbenzyl chloride No good library match No good library match N,N-dimethyltetradecanamide No good library match Centrimonium Bromide Lidocaine No good library match Dibutyl phthalate No good library match No good library match No good library match Bis(2-ethylhexyl)phthalate
86, 234
Lidocaine
rendered the IOL material hydrophilic and readily permeable to water molecules than to surgery or perioperative medications. The 2 patients were operated on by different surgeons (J.S. and N.A.) on different surgical lists using 2 OVD materials. Moreover, 1 patient had a similar procedure in the other eye but the IOL remained clear. Notably, a chromatographic peak for lidocaine was detected in the extract prepared from the lens suspension
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liquid of the explanted IOL but not in the blank water extract, which indicates that it was not an analytical artifact. Although this does not necessarily suggest a causal relationship to the opacification, it concurs with the suggestion by Kershner.23 Opacification related to deposits from silicone oil,24 an ophthalmic ointment15 as well as systemic medications such as amiodarone25 and rifabutin26 have been described. Most published cases describe clinically insignificant opacification that did not require explantation, and several factors seem to affect the patient’s need for explantation, including the magnitude of the opacity, the patient’s lifestyle, and perhaps the preoperative visual acuity. Our cases suggest that the optical design of the IOL through its effect on visual functions other than visual acuity may be an important determinant of whether the patient will need explantation; 1 of our patients required explantation despite relatively good visual acuity. Perhaps the reduction in contrast sensitivity, a function that is already compromised because of the optical design of the multifocal IOL, is probably the main incentive for explantation by patients with these IOLs. Although it has a potentially severe effect on vision, opacification of silicone IOLs is a rare complication. Recent estimates suggest an incidence of approximately 3 in 1 000 000 for AMO silicone IOLs (Tanaka et al.10) and 1 in 10 000 for the SA40N (personal communication). Clinically significant opacification remains more rare. No case of explantation of 3-piece silicone IOLs, including the SA40N, has been reported in the most recent survey by the American Society of Cataract and Refractive Surgery and the European Society of Cataract and Refractive Surgeons (N. Mamalis, et al. ‘‘Survey of Foldable IOLs Requiring Explantation or Secondary Intervention: 2005 Update,’’ presented at the XXIVth Congress of the European Society of Cataract and Refractive Surgeons, London, United Kingdom, September 2006). In conclusion, we have reported the opacification of 2 Array SA40N silicone multifocal IOLs, a phenomenon that has been seen in other silicone IOLs and appears to be related to an aberrant increase in the hydrophilicity of the silicone material of the optic. The effect of IOL opacification on visual acuity and contrast sensitivity functions may lead to more likelihood of patients with multifocal IOLs requiring explantation. Although the opacification is rare, further investigations are needed to identify the exact cause and reduce or even prevent its occurrence and thereby improve the overall compatibility and outcome with these IOLs.
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