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Interlenticular opacification: clinicopathological correlation of a complication of posterior chamber piggyback intraocular lenses
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Interlenticular opacification: Clinicopathological correlation of a complication of posterior chamber piggyback intraocular lenses Johnny L. Gayton, MD, David J. Apple, MD, Qun Peng, MD, Nithi Visessook, MD, Val Sanders, CRA, COT, Liliana Werner, MD, PhD, Suresh K. Pandey, MD, Marcela Escobar-Gomez, MD, Daphne S.M. Hoddinott, Michelle Van Der Karr ABSTRACT Purpose: To present a clinicopathological correlation of 2 pairs of piggyback posterior chamber intraocular lenses (PC IOLs) explanted because of opacification between the lens optics. Setting: Gayton Health Center, Eyesight Associates of Middle Georgia, Warner Robins, Georgia, and Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. Methods: Two pairs of piggyback AcrySof姞 lenses were explanted from 2 patients with significant visual loss related to opacification between the optics. They were submitted for pathological analysis. Gross and histopathological examinations were performed, and photomicroscopy was used to document the results. Results: Gross examination showed accumulation of a membrane-like white material between the lenses. Histopathological examination revealed that the tissue consisted of retained/proliferative lens epithelial cells (bladder cells or pearls) mixed with lens cortical material. Conclusion: Piggyback PC IOLs were explanted in 2 cases because of a newly described complication, interlenticular opacification. Three surgical means may help prevent this complication: meticulous cortical cleanup, especially in the equatorial region; creation of a relatively large continuous curvilinear capsulorhexis to sequester retained cells peripheral to the IOL optic within the equatorial fornix; insertion of the posterior IOL in the capsular bag and the anterior IOL in the ciliary sulcus to isolate retained cells from the interlenticular space. J Cataract Refract Surg 2000; 26:330 –336 © 2000 ASCRS and ESCRS
© 2000 ASCRS and ESCRS Published by Elsevier Science Inc.
0886-3350/00/$–see front matter PII S0886-3350(99)00433-2
INTERLENTICULAR OPACIFICATION WITH PIGGYBACK IOL
T
he implantation of 2 or more posterior chamber intraocular lenses (IOLs) (polypseudophakia or piggyback lenses) was introduced by Gayton and Sanders in 1993.1 The purposes of piggyback IOLs are to provide adequate pseudophakic optical correction in patients requiring high IOL power and to allow secondary correction of an undesirable optical result following cataract extraction with IOL implantation. It has been successful in patients with extremely high hyperopia, myopia, and overcorrected pseudophakia using IOLs of various optic materials, including poly(methyl methacrylate) (PMMA), silicone, and hydrophobic acrylic.1– 8 One of us (J.L.G.) has implanted piggyback IOLs in 70 eyes and followed the patients for at least 2 years. Postoperative opacification between the opposing surfaces of the piggyback implants has been noted in 23 eyes (32.8%). The opacification was noted only in primary implantation in which both IOLs were implanted in the bag. In 1 eye with 2 PMMA lenses, the membrane formation was observed between the optics in association with complicated glaucoma and chronic uveitis. The membrane was easily stripped from between the lenses. Twenty-one of the remaining 22 cases had piggyback acrylic lenses; 2 required explantation and lens exchange. We report the first clinicopathological correlation of opacification between piggyback IOLs. Synonyms for this condition include interlenticular opacification and interpseudophakic opacification, and related conditions include interpseudophakos Elschnig pearls.9 Accepted for publication December 21, 1999. From Gayton Health Center, Eyesight Associates of Middle Georgia, Warner Robins, Georgia (Gayton, Sanders), Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina (Apple, Peng, Visessook, Werner, Pandey, Escobar-Gomez, Hoddinott), and Ophthalmic Research Associates, Evanston, Illinois (Van Der Karr), USA. Presented in part at the Symposium on Cataract, IOL and Refractive Surgery, Seattle, Washington, USA, April 1999. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York, USA. None of the authors has a financial or proprietary interest in any product mentioned. Reprints requests to Johnny L. Gayton, MD, 216 Corder Road, PO Box 6479, Warner Robins, GA 31088 –3604, USA.
Patients and Methods Clinical Case Reports Case 1. A 77-year-old woman presented for cataract surgery in 1996 with a refraction of ⫹7.00 ⫹1.75 ⫻ 180 in the right eye and ⫹5.75 ⫹1.75 ⫻ 1 in the left eye. She had phacoemulsification in the right eye with implantation of 2 piggyback AcrySof威 IOLs (Alcon Laboratories) in the capsular bag. The anterior optic edge was covered by the cut edge of the anterior capsule over 360 degrees. Five months later, refraction was –2.50 ⫹2.25 ⫻ 178 with a best corrected visual acuity (BCVA) of 20/30. Opacification between the 2 IOLs was first noted 27 months postoperatively (Figure 1). At that time, refraction was plano ⫹1.75 ⫻ 180 and BCVA, 20/40. The piggyback IOLs were removed and exchanged with 2 biconvex PMMA lenses. The explanted lenses were tightly fused and could not be separated. They were submitted and processed for pathological examination at the Center for Research on Ocular Therapeutics and Biodevices. Three weeks after the exchange, refraction was – 6.00 ⫹1.50 ⫻ 15 and BCVA, 20/60. A second IOL exchange of the front (anterior) piggyback lens was performed 3 weeks after the first exchange, yielding a refraction 1 week later of –1.25 ⫹1.00 ⫻ 18, a BCVA of 20/50, and an uncorrected visual acuity (UCVA) of 20/200. The patient had a neodymium:YAG (Nd:YAG) posterior capsulotomy 2 months after the latter exchange. One week after the capsulotomy, refraction was – 0.25 ⫹1.50 ⫻ 11 with a BCVA of 20/40 and UCVA of 20/40. Case 2. An 80-year-old man presented for cataract surgery in 1996. Preoperative refraction in the right eye was ⫹6.00 ⫹0.75 ⫻ 105 with a BCVA of 20/70. Refraction in the left eye was ⫹6.25 ⫹0.50 ⫻ 10 with a BCVA of 20/40. Phacoemulsification with piggyback implantation of 2 AcrySof IOLs in the capsular bag was performed in both eyes. The anterior lens edge was covered by the cut edge of the anterior capsule over 360 degrees. Two months postoperatively, refraction in the right eye was –3.25 ⫹1.75 ⫻ 103, BCVA was 20/25, and UCVA was 20/80. In the left eye, refraction was – 0.75 ⫹0.50 ⫻ 180, BCVA was 20/25, and UCVA was 20/25. Twenty-nine months postoperatively, slitlamp
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Two months after the capsulotomy, refraction in the right eye was –1.75 ⫹0.75 ⫻ 58 with a BCVA of 20/25 and UCVA of 20/70. The lenses explanted from the right eye were submitted and processed for pathological examination at the Center for Research on Ocular Therapeutics and Biodevices. The patient declined surgical intervention in the left eye at that time.
Figure 1. (Gayton) Slitlamp photograph of the right eye in Case 1 after pupil dilation shows the opacification between the lenses 27 months postoperatively.
examination revealed membrane formation between the IOLs in both eyes. At that time, refraction was ⫹0.25 ⫹1.00 ⫻ 110 in the right eye and ⫹1.25 ⫹0.75 ⫻ 40 in the left eye; BCVA was 20/50 and 20/30 and UCVA, 20/80 and 20/100, respectively. An attempt was made to remove the interlenticular opacity by separating the lenses and aspirating the material. Efforts at aspiration and polishing were unsuccessful. The 2 IOLs in the right eye were removed by secondary lens exchange while the lenses in the left eye remained intact. Three weeks after IOL exchange, refraction in the right eye was –3.75 ⫹0.50 ⫻ 180 with a BCVA of 20/30 and UCVA of 20/200. Six weeks after the IOL exchange, the patient had an Nd:YAG laser posterior capsulotomy.
Pathological Examination of Explanted IOLs Gross examination of the explanted piggyback lenses was performed under a surgical microscope (Leica-Wild Model M8), and gross photographs were taken with a camera attached to the microscope. The lenses were processed for histopathological examination (dehydration in ethanol; embedding in paraffin; section). Hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome were used to stain the tissue sections. Photomicrographs were taken with a camera (Olympus, Optical Co. Ltd.) fitted to a light microscope.
Results Case 1 Gross examination demonstrated that the 2 piggyback lenses were fused together by a white membranelike material about 5.0 mm thick (Figure 2). The opacification caused by the material in the interlenticular space was not total and intervening clear areas were noted, including a 1.0 mm diameter clear zone in the center where the 2 lenses came into close apposition. At this level, a depression on the outer (external) surfaces of
Figure 2. (Gayton) Case 1: Gross photographs of the explanted pair of piggyback IOLs. A: Anterior–posterior (frontal) view. Note the white opacification between the 2 IOLs. There are some clear areas, including the central zone, where a depression on the anterior surface of the anterior lens can be seen. B: Sagittal view. The membrane-like formation is 5.0 mm thick.
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Figure 3. (Gayton) Case 1: Photomicrograph of a region between the 2 lenses (interlenticular space) with minimal involvement by the membrane-like formation. There are few cortical remnants on the lenses’ apposing surfaces, but most of the space is clear (A ⫽ anterior IOL; P ⫽ posterior IOL) (hematoxylin & eosin; original magnification ⫻100).
Figure 4. (Gayton) Case 1: Photomicrograph of another region between the 2 lenses (interlenticular space) strongly involved by the membrane-like formation showing exuberant presence of retained cortex and swollen, proliferative bladder (Wedl) cells, or pearls. The basophilic staining nuclei of the bladder cells are clearly visible (hematoxylin & eosin; original magnification ⫻400).
both lenses was also observed (Figure 2, A). Separation of the lenses was attempted without success. Histological sections were then obtained from the whole specimen (both IOLs and the membrane formation). Light microscopy revealed that the thick white membrane was composed of clusters of retained/proliferating swollen lens epithelial cells (LECs) (bladder/Wedl cells or pearls) interspersed in a homogeneous eosinophilic material, recognizable as lens cortical material (Figures 3 and 4). Masson’s trichrome stain showed no evidence of fibrosis (Figure 5). Figure 5. (Gayton) Case 1: Photomicrograph of the opacified interlenticular space. Masson’s trichrome stain shows no evidence of fibrous tissue, (A ⫽ anterior IOL; P ⫽ posterior IOL) (original magnification ⫻100).
Case 2 The 2 piggyback IOLs from this case had been separated and the lenses were submitted individually for
Figure 6. (Gayton) Case 2: Gross photographs (frontal view) of the 2 piggyback IOLs showing the clear central area where the 2 lenses came into contact. A: Anterior (front) IOL. B: Posterior (rear) IOL.
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Figure 7. (Gayton) Case 2: Photomicrographs taken at the posterior surface of the front (anterior) IOL. A: Note the presence of a monolayer of flat cuboidal cells (A ⫽ anterior IOL) (hematoxylin & eosin; original magnification ⫻400). Scattered, spindle-shaped cells (arrow) were also observed on the rear (posterior) surface of the same IOL (A ⫽ anterior IOL) (hematoxylin & eosin; original magnification ⫻400).
Figure 8. (Gayton) Case 2: Photomicrographs of areas with foci of retained lens cortex and bladder cells. Such areas were rare, and in general, the intervening interlenticular space was empty. A: Posterior surface of the front (anterior) IOL. B: Anterior surface of the back (posterior) (Masson’s trichrome; original magnification ⫻400).
Figure 9. (Gayton) Illustration showing 2 IOLs placed in the capsular bag. Note the potential ingrowth of LECs from the epithelial lens bow in the interlenticular space.
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pathological examination (Figure 6). One of the lens’ haptics had been amputated during surgical explantation (Figure 6, A). Frontal examination of both lenses revealed a white opacification with a 1.0 mm clear central zone corresponding to the site where the IOLs came into close apposition. Microscopic examination revealed that much of the opacification on the posterior surface of the front lens and anterior surface of the back lens consisted of a thin monolayer of retained LECs (Figure 7, A) or small, flat, spindle-shaped cells (Figure 7, B). Scattered small clusters of retained/proliferative cortex and pearls were also noted (Figure 8), but were not as prominent as seen in Case 1 (Figure 4).
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Discussion Opacification of the ocular media caused by proliferation of cells in the capsular bag remains the most frequent complication after cataract surgery. Classic posterior capsule opacification (PCO) is a well-known, intensely studied complication.10 –12 However, postoperative LEC proliferation is also involved in the pathogenesis of other relatively less known entities including anterior capsule opacification (ACO)13,14 and a newly described complication related to piggyback IOL implantation that we have named interlenticular opacification. In the normal, undisturbed lens, the epithelium is confined to the anterior surface and to the equatorial region and equatorial lens bow. It consists of a single row of cuboidal cells that can be divided into 2 biological zones: 1. The anterior– central zone (corresponding to the zone of the anterior lens capsule) consists of a monolayer of flat, cuboidal, relatively quiescent epithelial cells with minimal mitotic activity. The primary type of response of the anterior epithelial cells (A-cells) to any stimulus is to proliferate and form fibrous tissue by undergoing fibrous metaplasia. This process is primarily involved in the pathogenesis of ACO and also in a less commonly observed form of PCO: the fibrous type. 2. The second zone, which is of utmost importance in the pathogenesis of the pearl form of PCO, is a continuation of anterior lens cells around the equator, forming the equatorial lens bow (E-cells). Mitosis, cell division, and multiplication in this region are active. New lens fibers are continuously produced in this zone throughout one’s life. In this report, we describe a condition characterized by opacification in an anatomically intermediate site between the anterior and posterior capsules. Because the opacification occurred in the space between the 2 piggyback IOL optics, we termed this condition interlenticular opacification. There appears to be at least 2 forms of interlenticular opacification; namely, the pearl form, typically represented by Case 1, and a less well-understood form consisting primarily of an amorphous material with few or no cells. We recently analyzed an explanted pair of piggyback AcrySof lenses presenting the second form. In the 2 cases reported here, the opaque membranelike material localized between the piggyback lenses was histopathologically demonstrated to be composed of re-
tained/proliferative cortex and proliferating LECs, including bladder (Wedl) cells. This profile, noted particularly in Case 1, is virtually identical to the pathologic process seen in posterior subcapsular cataracts and the typical pearl form of PCO. The nature of the acrylic material may play a role in the outcome of this form of interlenticular opacification. According to the sandwich theory,15 a bioactivity-based explanation for PCO, if the IOL is of a bioactive material, it would allow a single LEC to bond to both the IOL and the posterior capsule. This would produce a sandwich pattern including the IOL, the cell monolayer, and the posterior capsule. The sealed sandwich structure might prevent further posterior epithelial ingrowth and PCO. AcrySof lenses have been found to present adhesive properties in vitro.16 When they are implanted in the capsular bag, the bioadhesion of the anterior surface of the front lens to the anterior capsule edge and of the posterior surface of the back lens to the posterior capsule prevents cell migration from the equatorial bow to the posterior capsule. This migration may be directed toward the interlenticular space (Figure 9). Even if the material’s high refractive index (1.55) allows the AcrySof to be thinner and flatter than PMMA or silicone IOLs,17 there is a potential space between the lenses placed in the capsular bag. Also, the adhesive nature of the AcrySof material seems to make the membranes difficult to remove by any surgical mean. Another complication related to piggyback lenses, also observed in the 2 cases reported here, is postoperative hyperopic shift. In the first case, 5 months after piggyback implantation, the refraction was –2.50 ⫹2.25 ⫻ 178; it was plano ⫹1.75 ⫻ 180 when the opacification was first observed. In the second case, 2 months after implantation, the refraction in the right eye was –3.25 ⫹1.75 ⫻ 103 and in the left eye, – 0.75 ⫹0.50 ⫻ 180. At the time the membrane formation was detected, the refraction changed to ⫹0.25 ⫹1.00 ⫻ 110 in the right eye and ⫹1.25 ⫹0.75 ⫻ 40 in the left eye. Shugar and Schwartz9 also report a clinically significant hyperopic shift between 1 and 2 years after implantation of piggyback IOLs. All eyes in their series had proliferating Elschnig pearls visible in the peripheral interface between the IOLs’ optics (interpseudophakos Elschnig pearls). According to the authors, the cellular material proliferating in the peripheral interface between the lenses appeared to cause posterior displace-
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ment of the posterior IOL. A second possible cause was the separation of the 2 optic surfaces peripherally, which could affect zonular tension and thus cause posterior displacement of the entire IOL/capsular bag complex. We believe that the depression on the surface of the lenses where they were in close apposition, as seen mainly in our Case 1, also had an influence on the changes in lens power. According to the proposed pathogenic mechanism of interlenticular opacification shown in Figure 9, an important surgical means of preventing this complication would be careful cortical cleanup, which can be enhanced by copious hydrodissection. This would help remove most remaining cells from the equatorial lens bow. In addition, other surgical means to prevent interlenticular opacification include the following: (1) Deviating from total bag-bag fixation by placing the posterior IOL in the bag and the anterior IOL in the sulcus. The bioadhesion of the AcrySof lens placed in the bag to the posterior aspect of the cut anterior continuous curvilinear capsulorhexis (CCC) edge isolates the lens equatorial bow from the interlenticular space. (2) Performing a CCC larger than the IOL optic. With a relatively small CCC, the entire capsule compartment is a closed system. The square edge of AcrySof lenses and the adhesion of the posterior IOL optic to the posterior capsule prevent residual LECs from the equatorial bow from migrating and proliferating onto the posterior capsule. This may explain why the growth of cells is more confined to the space between the IOLs. If the CCC is made larger than the optic, the cut anterior CCC edge can adhere to the posterior capsule and thus sequester the residual cells in the fornix (J.L. Gayton, MD, D.J. Apple, MD, “Refractive Stability and Long-Term Interlenticular Membrane Formation of Piggyback Intraocular Implants,” presented at the annual meeting of the American Academy of Ophthalmology, Orlando, Florida, USA, October 1999). In summary, we described a new form of opacification in the capsular bag caused by LEC migration and proliferation into the space between 2 piggyback IOLs—interlenticular opacification. The technique of piggyback IOLs is used relatively frequently now but will increase in the coming decades. The lenses also have application in the developing world. Therefore, an awareness of this new condition is warranted. 336
References 1. Gayton JL, Sanders VN. Implanting two posterior chamber intraocular lenses in a case of microphthalmos. J Cataract Refract Surg 1993; 19:776 –777 2. Holladay JT, Gills JP, Leidlein J, Cherchio M. Achieving emmetropia in extremely short eyes with two piggyback posterior chamber intraocular lenses. Ophthalmology 1996; 103:1118 –1123 3. Gills JP. Piggyback minus-power lens implantation in keratoconus. J Cataract Refract Surg 1998; 24:566 –568 4. Gills JP, Gayton JL, Raanan M. Multiple intraocular lens implantation. In: Gills JP, Fenzl R, Martin RG, eds, Cataract Surgery; the State of the Art. Thorofare, NJ, Slack, 1998; 183–195 5. Mittelviefhaus H. Piggyback intraocular lens with exchangeable optic. J Cataract Refract Surg 1996; 22:676 – 681 6. Masket S. Piggyback intraocular lens implantation. J Cataract Refract Surg 1998; 24:569 –570 7. Shugar JK, Lewis C, Lee A. Implantation of multiple foldable acrylic posterior chamber lenses in the capsular bag for high hyperopia. J Cataract Refract Surg 1996; 22:1368 –1372 8. Fenzl RE, Gills JP, Cherchio M. Refractive and visual outcome of hyperopic cataract cases operated on before and after implementation of the Holladay II formula. Ophthalmology 1998; 105:1759 –1764 9. Shugar JK, Schwartz T. Interpseudophakos Elschnig pearls associated with late hyperopic shift: a complication of piggyback posterior chamber intraocular lens implantation. J Cataract Refract Surg 1999; 25:863– 867 10. Apple DJ, Solomon KD, Tetz MR, et al. Posterior capsule opacification. Surv Ophthalmol 1992; 37:73–116 11. Schaumberg DA, Dana MR, Christen WG, Glynn RJ. A systematic overview of the incidence of posterior capsule opacification. Ophthalmology 1998; 105:1213–1221 12. Nishi O. Posterior capsule opacification. Part 1: experimental investigations. J Cataract Refract Surg 1999; 25: 106 –117 13. Davison JA. Capsule contraction syndrome. J Cataract Refract Surg 1993; 19:582–589 14. Werner L, Pandey SK, Escobar-Gomez M, et al. Anterior capsular opacification: a histopathological study comparing different IOL styles. Ophthalmology 2000; 107:463– 471 15. Linnola RJ. Sandwich theory: bioactivity-based explanation for posterior capsule opacification. J Cataract Refract Surg 1997; 23:1539 –1542 16. Nagata T, Minakata A, Watanabe I. Adhesiveness of AcrySof to a collagen film. J Cataract Refract Surg 1998; 24:367–370 17. Anderson C, Koch DD, Green G, et al. Alcon AcrySofTM acrylic intraocular lens. In: Martin RG, Gills JP, Sanders DR, eds, Foldable Intraocular Lenses. Thorofare, NJ, Slack, 1993; 161–177
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Interlenticular opacification: Clinicopathological correlation of a complication of posterior chamber piggyback intraocular lenses Johnny L. Gayton, MD, David J. Apple, MD, Qun Peng, MD, Nithi Visessook, MD, Val Sanders, CRA, COT, Liliana Werner, MD, PhD, Suresh K. Pandey, MD, Marcela Escobar-Gomez, MD, Daphne S.M. Hoddinott, Michelle Van Der Karr ABSTRACT Purpose: To present a clinicopathological correlation of 2 pairs of piggyback posterior chamber intraocular lenses (PC IOLs) explanted because of opacification between the lens optics. Setting: Gayton Health Center, Eyesight Associates of Middle Georgia, Warner Robins, Georgia, and Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. Methods: Two pairs of piggyback AcrySof姞 lenses were explanted from 2 patients with significant visual loss related to opacification between the optics. They were submitted for pathological analysis. Gross and histopathological examinations were performed, and photomicroscopy was used to document the results. Results: Gross examination showed accumulation of a membrane-like white material between the lenses. Histopathological examination revealed that the tissue consisted of retained/proliferative lens epithelial cells (bladder cells or pearls) mixed with lens cortical material. Conclusion: Piggyback PC IOLs were explanted in 2 cases because of a newly described complication, interlenticular opacification. Three surgical means may help prevent this complication: meticulous cortical cleanup, especially in the equatorial region; creation of a relatively large continuous curvilinear capsulorhexis to sequester retained cells peripheral to the IOL optic within the equatorial fornix; insertion of the posterior IOL in the capsular bag and the anterior IOL in the ciliary sulcus to isolate retained cells from the interlenticular space. J Cataract Refract Surg 2000; 26:330 –336 © 2000 ASCRS and ESCRS
© 2000 ASCRS and ESCRS Published by Elsevier Science Inc.
0886-3350/00/$–see front matter PII S0886-3350(99)00433-2
INTERLENTICULAR OPACIFICATION WITH PIGGYBACK IOL
T
he implantation of 2 or more posterior chamber intraocular lenses (IOLs) (polypseudophakia or piggyback lenses) was introduced by Gayton and Sanders in 1993.1 The purposes of piggyback IOLs are to provide adequate pseudophakic optical correction in patients requiring high IOL power and to allow secondary correction of an undesirable optical result following cataract extraction with IOL implantation. It has been successful in patients with extremely high hyperopia, myopia, and overcorrected pseudophakia using IOLs of various optic materials, including poly(methyl methacrylate) (PMMA), silicone, and hydrophobic acrylic.1– 8 One of us (J.L.G.) has implanted piggyback IOLs in 70 eyes and followed the patients for at least 2 years. Postoperative opacification between the opposing surfaces of the piggyback implants has been noted in 23 eyes (32.8%). The opacification was noted only in primary implantation in which both IOLs were implanted in the bag. In 1 eye with 2 PMMA lenses, the membrane formation was observed between the optics in association with complicated glaucoma and chronic uveitis. The membrane was easily stripped from between the lenses. Twenty-one of the remaining 22 cases had piggyback acrylic lenses; 2 required explantation and lens exchange. We report the first clinicopathological correlation of opacification between piggyback IOLs. Synonyms for this condition include interlenticular opacification and interpseudophakic opacification, and related conditions include interpseudophakos Elschnig pearls.9 Accepted for publication December 21, 1999. From Gayton Health Center, Eyesight Associates of Middle Georgia, Warner Robins, Georgia (Gayton, Sanders), Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina (Apple, Peng, Visessook, Werner, Pandey, Escobar-Gomez, Hoddinott), and Ophthalmic Research Associates, Evanston, Illinois (Van Der Karr), USA. Presented in part at the Symposium on Cataract, IOL and Refractive Surgery, Seattle, Washington, USA, April 1999. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., New York, New York, USA. None of the authors has a financial or proprietary interest in any product mentioned. Reprints requests to Johnny L. Gayton, MD, 216 Corder Road, PO Box 6479, Warner Robins, GA 31088 –3604, USA.
Patients and Methods Clinical Case Reports Case 1. A 77-year-old woman presented for cataract surgery in 1996 with a refraction of ⫹7.00 ⫹1.75 ⫻ 180 in the right eye and ⫹5.75 ⫹1.75 ⫻ 1 in the left eye. She had phacoemulsification in the right eye with implantation of 2 piggyback AcrySof威 IOLs (Alcon Laboratories) in the capsular bag. The anterior optic edge was covered by the cut edge of the anterior capsule over 360 degrees. Five months later, refraction was –2.50 ⫹2.25 ⫻ 178 with a best corrected visual acuity (BCVA) of 20/30. Opacification between the 2 IOLs was first noted 27 months postoperatively (Figure 1). At that time, refraction was plano ⫹1.75 ⫻ 180 and BCVA, 20/40. The piggyback IOLs were removed and exchanged with 2 biconvex PMMA lenses. The explanted lenses were tightly fused and could not be separated. They were submitted and processed for pathological examination at the Center for Research on Ocular Therapeutics and Biodevices. Three weeks after the exchange, refraction was – 6.00 ⫹1.50 ⫻ 15 and BCVA, 20/60. A second IOL exchange of the front (anterior) piggyback lens was performed 3 weeks after the first exchange, yielding a refraction 1 week later of –1.25 ⫹1.00 ⫻ 18, a BCVA of 20/50, and an uncorrected visual acuity (UCVA) of 20/200. The patient had a neodymium:YAG (Nd:YAG) posterior capsulotomy 2 months after the latter exchange. One week after the capsulotomy, refraction was – 0.25 ⫹1.50 ⫻ 11 with a BCVA of 20/40 and UCVA of 20/40. Case 2. An 80-year-old man presented for cataract surgery in 1996. Preoperative refraction in the right eye was ⫹6.00 ⫹0.75 ⫻ 105 with a BCVA of 20/70. Refraction in the left eye was ⫹6.25 ⫹0.50 ⫻ 10 with a BCVA of 20/40. Phacoemulsification with piggyback implantation of 2 AcrySof IOLs in the capsular bag was performed in both eyes. The anterior lens edge was covered by the cut edge of the anterior capsule over 360 degrees. Two months postoperatively, refraction in the right eye was –3.25 ⫹1.75 ⫻ 103, BCVA was 20/25, and UCVA was 20/80. In the left eye, refraction was – 0.75 ⫹0.50 ⫻ 180, BCVA was 20/25, and UCVA was 20/25. Twenty-nine months postoperatively, slitlamp
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Two months after the capsulotomy, refraction in the right eye was –1.75 ⫹0.75 ⫻ 58 with a BCVA of 20/25 and UCVA of 20/70. The lenses explanted from the right eye were submitted and processed for pathological examination at the Center for Research on Ocular Therapeutics and Biodevices. The patient declined surgical intervention in the left eye at that time.
Figure 1. (Gayton) Slitlamp photograph of the right eye in Case 1 after pupil dilation shows the opacification between the lenses 27 months postoperatively.
examination revealed membrane formation between the IOLs in both eyes. At that time, refraction was ⫹0.25 ⫹1.00 ⫻ 110 in the right eye and ⫹1.25 ⫹0.75 ⫻ 40 in the left eye; BCVA was 20/50 and 20/30 and UCVA, 20/80 and 20/100, respectively. An attempt was made to remove the interlenticular opacity by separating the lenses and aspirating the material. Efforts at aspiration and polishing were unsuccessful. The 2 IOLs in the right eye were removed by secondary lens exchange while the lenses in the left eye remained intact. Three weeks after IOL exchange, refraction in the right eye was –3.75 ⫹0.50 ⫻ 180 with a BCVA of 20/30 and UCVA of 20/200. Six weeks after the IOL exchange, the patient had an Nd:YAG laser posterior capsulotomy.
Pathological Examination of Explanted IOLs Gross examination of the explanted piggyback lenses was performed under a surgical microscope (Leica-Wild Model M8), and gross photographs were taken with a camera attached to the microscope. The lenses were processed for histopathological examination (dehydration in ethanol; embedding in paraffin; section). Hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome were used to stain the tissue sections. Photomicrographs were taken with a camera (Olympus, Optical Co. Ltd.) fitted to a light microscope.
Results Case 1 Gross examination demonstrated that the 2 piggyback lenses were fused together by a white membranelike material about 5.0 mm thick (Figure 2). The opacification caused by the material in the interlenticular space was not total and intervening clear areas were noted, including a 1.0 mm diameter clear zone in the center where the 2 lenses came into close apposition. At this level, a depression on the outer (external) surfaces of
Figure 2. (Gayton) Case 1: Gross photographs of the explanted pair of piggyback IOLs. A: Anterior–posterior (frontal) view. Note the white opacification between the 2 IOLs. There are some clear areas, including the central zone, where a depression on the anterior surface of the anterior lens can be seen. B: Sagittal view. The membrane-like formation is 5.0 mm thick.
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Figure 3. (Gayton) Case 1: Photomicrograph of a region between the 2 lenses (interlenticular space) with minimal involvement by the membrane-like formation. There are few cortical remnants on the lenses’ apposing surfaces, but most of the space is clear (A ⫽ anterior IOL; P ⫽ posterior IOL) (hematoxylin & eosin; original magnification ⫻100).
Figure 4. (Gayton) Case 1: Photomicrograph of another region between the 2 lenses (interlenticular space) strongly involved by the membrane-like formation showing exuberant presence of retained cortex and swollen, proliferative bladder (Wedl) cells, or pearls. The basophilic staining nuclei of the bladder cells are clearly visible (hematoxylin & eosin; original magnification ⫻400).
both lenses was also observed (Figure 2, A). Separation of the lenses was attempted without success. Histological sections were then obtained from the whole specimen (both IOLs and the membrane formation). Light microscopy revealed that the thick white membrane was composed of clusters of retained/proliferating swollen lens epithelial cells (LECs) (bladder/Wedl cells or pearls) interspersed in a homogeneous eosinophilic material, recognizable as lens cortical material (Figures 3 and 4). Masson’s trichrome stain showed no evidence of fibrosis (Figure 5). Figure 5. (Gayton) Case 1: Photomicrograph of the opacified interlenticular space. Masson’s trichrome stain shows no evidence of fibrous tissue, (A ⫽ anterior IOL; P ⫽ posterior IOL) (original magnification ⫻100).
Case 2 The 2 piggyback IOLs from this case had been separated and the lenses were submitted individually for
Figure 6. (Gayton) Case 2: Gross photographs (frontal view) of the 2 piggyback IOLs showing the clear central area where the 2 lenses came into contact. A: Anterior (front) IOL. B: Posterior (rear) IOL.
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Figure 7. (Gayton) Case 2: Photomicrographs taken at the posterior surface of the front (anterior) IOL. A: Note the presence of a monolayer of flat cuboidal cells (A ⫽ anterior IOL) (hematoxylin & eosin; original magnification ⫻400). Scattered, spindle-shaped cells (arrow) were also observed on the rear (posterior) surface of the same IOL (A ⫽ anterior IOL) (hematoxylin & eosin; original magnification ⫻400).
Figure 8. (Gayton) Case 2: Photomicrographs of areas with foci of retained lens cortex and bladder cells. Such areas were rare, and in general, the intervening interlenticular space was empty. A: Posterior surface of the front (anterior) IOL. B: Anterior surface of the back (posterior) (Masson’s trichrome; original magnification ⫻400).
Figure 9. (Gayton) Illustration showing 2 IOLs placed in the capsular bag. Note the potential ingrowth of LECs from the epithelial lens bow in the interlenticular space.
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pathological examination (Figure 6). One of the lens’ haptics had been amputated during surgical explantation (Figure 6, A). Frontal examination of both lenses revealed a white opacification with a 1.0 mm clear central zone corresponding to the site where the IOLs came into close apposition. Microscopic examination revealed that much of the opacification on the posterior surface of the front lens and anterior surface of the back lens consisted of a thin monolayer of retained LECs (Figure 7, A) or small, flat, spindle-shaped cells (Figure 7, B). Scattered small clusters of retained/proliferative cortex and pearls were also noted (Figure 8), but were not as prominent as seen in Case 1 (Figure 4).
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Discussion Opacification of the ocular media caused by proliferation of cells in the capsular bag remains the most frequent complication after cataract surgery. Classic posterior capsule opacification (PCO) is a well-known, intensely studied complication.10 –12 However, postoperative LEC proliferation is also involved in the pathogenesis of other relatively less known entities including anterior capsule opacification (ACO)13,14 and a newly described complication related to piggyback IOL implantation that we have named interlenticular opacification. In the normal, undisturbed lens, the epithelium is confined to the anterior surface and to the equatorial region and equatorial lens bow. It consists of a single row of cuboidal cells that can be divided into 2 biological zones: 1. The anterior– central zone (corresponding to the zone of the anterior lens capsule) consists of a monolayer of flat, cuboidal, relatively quiescent epithelial cells with minimal mitotic activity. The primary type of response of the anterior epithelial cells (A-cells) to any stimulus is to proliferate and form fibrous tissue by undergoing fibrous metaplasia. This process is primarily involved in the pathogenesis of ACO and also in a less commonly observed form of PCO: the fibrous type. 2. The second zone, which is of utmost importance in the pathogenesis of the pearl form of PCO, is a continuation of anterior lens cells around the equator, forming the equatorial lens bow (E-cells). Mitosis, cell division, and multiplication in this region are active. New lens fibers are continuously produced in this zone throughout one’s life. In this report, we describe a condition characterized by opacification in an anatomically intermediate site between the anterior and posterior capsules. Because the opacification occurred in the space between the 2 piggyback IOL optics, we termed this condition interlenticular opacification. There appears to be at least 2 forms of interlenticular opacification; namely, the pearl form, typically represented by Case 1, and a less well-understood form consisting primarily of an amorphous material with few or no cells. We recently analyzed an explanted pair of piggyback AcrySof lenses presenting the second form. In the 2 cases reported here, the opaque membranelike material localized between the piggyback lenses was histopathologically demonstrated to be composed of re-
tained/proliferative cortex and proliferating LECs, including bladder (Wedl) cells. This profile, noted particularly in Case 1, is virtually identical to the pathologic process seen in posterior subcapsular cataracts and the typical pearl form of PCO. The nature of the acrylic material may play a role in the outcome of this form of interlenticular opacification. According to the sandwich theory,15 a bioactivity-based explanation for PCO, if the IOL is of a bioactive material, it would allow a single LEC to bond to both the IOL and the posterior capsule. This would produce a sandwich pattern including the IOL, the cell monolayer, and the posterior capsule. The sealed sandwich structure might prevent further posterior epithelial ingrowth and PCO. AcrySof lenses have been found to present adhesive properties in vitro.16 When they are implanted in the capsular bag, the bioadhesion of the anterior surface of the front lens to the anterior capsule edge and of the posterior surface of the back lens to the posterior capsule prevents cell migration from the equatorial bow to the posterior capsule. This migration may be directed toward the interlenticular space (Figure 9). Even if the material’s high refractive index (1.55) allows the AcrySof to be thinner and flatter than PMMA or silicone IOLs,17 there is a potential space between the lenses placed in the capsular bag. Also, the adhesive nature of the AcrySof material seems to make the membranes difficult to remove by any surgical mean. Another complication related to piggyback lenses, also observed in the 2 cases reported here, is postoperative hyperopic shift. In the first case, 5 months after piggyback implantation, the refraction was –2.50 ⫹2.25 ⫻ 178; it was plano ⫹1.75 ⫻ 180 when the opacification was first observed. In the second case, 2 months after implantation, the refraction in the right eye was –3.25 ⫹1.75 ⫻ 103 and in the left eye, – 0.75 ⫹0.50 ⫻ 180. At the time the membrane formation was detected, the refraction changed to ⫹0.25 ⫹1.00 ⫻ 110 in the right eye and ⫹1.25 ⫹0.75 ⫻ 40 in the left eye. Shugar and Schwartz9 also report a clinically significant hyperopic shift between 1 and 2 years after implantation of piggyback IOLs. All eyes in their series had proliferating Elschnig pearls visible in the peripheral interface between the IOLs’ optics (interpseudophakos Elschnig pearls). According to the authors, the cellular material proliferating in the peripheral interface between the lenses appeared to cause posterior displace-
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ment of the posterior IOL. A second possible cause was the separation of the 2 optic surfaces peripherally, which could affect zonular tension and thus cause posterior displacement of the entire IOL/capsular bag complex. We believe that the depression on the surface of the lenses where they were in close apposition, as seen mainly in our Case 1, also had an influence on the changes in lens power. According to the proposed pathogenic mechanism of interlenticular opacification shown in Figure 9, an important surgical means of preventing this complication would be careful cortical cleanup, which can be enhanced by copious hydrodissection. This would help remove most remaining cells from the equatorial lens bow. In addition, other surgical means to prevent interlenticular opacification include the following: (1) Deviating from total bag-bag fixation by placing the posterior IOL in the bag and the anterior IOL in the sulcus. The bioadhesion of the AcrySof lens placed in the bag to the posterior aspect of the cut anterior continuous curvilinear capsulorhexis (CCC) edge isolates the lens equatorial bow from the interlenticular space. (2) Performing a CCC larger than the IOL optic. With a relatively small CCC, the entire capsule compartment is a closed system. The square edge of AcrySof lenses and the adhesion of the posterior IOL optic to the posterior capsule prevent residual LECs from the equatorial bow from migrating and proliferating onto the posterior capsule. This may explain why the growth of cells is more confined to the space between the IOLs. If the CCC is made larger than the optic, the cut anterior CCC edge can adhere to the posterior capsule and thus sequester the residual cells in the fornix (J.L. Gayton, MD, D.J. Apple, MD, “Refractive Stability and Long-Term Interlenticular Membrane Formation of Piggyback Intraocular Implants,” presented at the annual meeting of the American Academy of Ophthalmology, Orlando, Florida, USA, October 1999). In summary, we described a new form of opacification in the capsular bag caused by LEC migration and proliferation into the space between 2 piggyback IOLs—interlenticular opacification. The technique of piggyback IOLs is used relatively frequently now but will increase in the coming decades. The lenses also have application in the developing world. Therefore, an awareness of this new condition is warranted. 336
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