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Figure 1.
Design and placement of the capsular adhesion–preventing ring (CAPR). A, Schematic diagrams of the CAPR showing its 4 grooves and 4 holes. The inner and outer diameters of the ring are 6.5 and 8.5 mm, respectively. B, In-the-bag implantation of both the CAPR and an intraocular lens (IOL). The anterior and posterior capsules are kept separated from each other by the CAPR. CCC indicates continuous curvilinear capsulorrhexis.

Design and placement of the capsular adhesion–preventing ring (CAPR). A, Schematic diagrams of the CAPR showing its 4 grooves and 4 holes. The inner and outer diameters of the ring are 6.5 and 8.5 mm, respectively. B, In-the-bag implantation of both the CAPR and an intraocular lens (IOL). The anterior and posterior capsules are kept separated from each other by the CAPR. CCC indicates continuous curvilinear capsulorrhexis.

Figure 2.
Histologic photographs (toluidine blue; bar represents 500 μm). In the capsular adhesion–preventing ring (CAPR) group (n = 5), both a polymethyl methacrylate intraocular lens and the CAPR were implanted in the capsular bag (left panels). Only the intraocular lens was implanted in the 5 fellow eyes as controls (right panels). Note the significant difference in thickness of the posterior capsule between the groups (arrowheads). Massive regeneration of lens fiber in the capsular bag, in which complete anteroposterior capsular adhesion occurred at the margin of the continuous curvilinear capsulorrhexis, was observed in each control eye. Strikingly, neither anteroposterior capsular adhesion nor regeneration of lens fiber occurred in 2 eyes with the CAPR (A and B; asterisks indicate the CAPR in all CAPR group images). An anteroposterior capsular adhesion peripheral to the CAPR appeared in 2 eyes (C and D), causing lens fiber regeneration in the closed space. Only 1 eye in the CAPR group (E) showed massive regeneration of lens fiber invading beneath the intraocular lens optic, although the center of the posterior capsule was still clear.

Histologic photographs (toluidine blue; bar represents 500 μm). In the capsular adhesion–preventing ring (CAPR) group (n = 5), both a polymethyl methacrylate intraocular lens and the CAPR were implanted in the capsular bag (left panels). Only the intraocular lens was implanted in the 5 fellow eyes as controls (right panels). Note the significant difference in thickness of the posterior capsule between the groups (arrowheads). Massive regeneration of lens fiber in the capsular bag, in which complete anteroposterior capsular adhesion occurred at the margin of the continuous curvilinear capsulorrhexis, was observed in each control eye. Strikingly, neither anteroposterior capsular adhesion nor regeneration of lens fiber occurred in 2 eyes with the CAPR (A and B; asterisks indicate the CAPR in all CAPR group images). An anteroposterior capsular adhesion peripheral to the CAPR appeared in 2 eyes (C and D), causing lens fiber regeneration in the closed space. Only 1 eye in the CAPR group (E) showed massive regeneration of lens fiber invading beneath the intraocular lens optic, although the center of the posterior capsule was still clear.

Table. 
Scores on PCO Measures
Scores on PCO Measures
1.
Chen  KHHarris  DLJoyce  NC TGF-β2 in aqueous humor suppresses S-phase entry in cultured corneal endothelial cells. Invest Ophthalmol Vis Sci 1999;40 (11) 2513- 2519
PubMed
2.
Kurosaka  DNagamoto  T Inhibitory effect of TGF-β2 in human aqueous humor on bovine lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 1994;35 (9) 3408- 3412
PubMed
3.
Weinsieder  ABriggs  RReddan  JRothstein  HWilson  DHarding  CV Induction of mitosis in ocular tissue by chemotoxic agents. Exp Eye Res 1975;20 (1) 33- 44
PubMedArticle
4.
Wallentin  NWickström  KLundberg  C Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 1998;39 (8) 1410- 1418
PubMed
5.
Reddan  JRWeinsieder  AWilson  D Aqueous humor from traumatized eyes triggers cell division in the epithelia of cultured lenses. Exp Eye Res 1979;28 (3) 267- 276
PubMedArticle
6.
Legler  UFApple  DJAssia  EIBluestein  ECCastaneda  VEMowbray  SL Inhibition of posterior capsule opacification: the effect of colchicines in a sustained drug delivery system. J Cataract Refract Surg 1993;19 (4) 462- 470
PubMedArticle
7.
Blomstedt  GFagerholm  PGallo  JPhilipson  B After-cataract in the rabbit eye following extracapsular cataract extraction: a wound healing reaction. Acta Ophthalmol Suppl 1987;18293- 99
PubMed
8.
Maruno  KALovicu  FJChamberlain  CG McAvoy  JW Apoptosis is a feature of TGF bet–induced cataract. Clin Exp Optom 2002;85 (2) 76- 82
PubMedArticle
9.
Nagamoto  THara  E Postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. J Cataract Refract Surg 1995;21 (2) 208- 211
PubMedArticle
10.
Ibaraki  NOhara  KMiyamoto  T Membranous outgrowth suggesting lens epithelial cell proliferation in pseudophakic eyes. Am J Ophthalmol 1995;119 (6) 706- 711
PubMed
11.
Kurosaka  DKato  K Membranous proliferation of lens epithelial cells on acrylic, silicone, and poly(methyl methacrylate) lenses. J Cataract Refract Surg 2001;27 (10) 1591- 1595
PubMedArticle
12.
Saika  SOhmi  SKanagawa  R  et al.  Lens epithelial cell outgrowth and matrix formation on intraocular lenses in rabbit eyes. J Cataract Refract Surg 1996;22 ((suppl 1)) 835- 840
PubMedArticle
13.
De Groot  VLeysen  INeuhann  TGobin  LTassignon  MJ One-year follow-up of bag-in-the-lens intraocular lens implantation in 60 eyes. J Cataract Refract Surg 2006;32 (10) 1632- 1637
PubMedArticle
14.
Tassignon  MJDe Veuster  IGodts  DKosec  DVan den Dooren  KGobin  L Bag-in-the-lens intraocular lens implantation in the pediatric eye. J Cataract Refract Surg 2007;33 (4) 611- 617
PubMedArticle
Laboratory Sciences
April 13, 2009

Inhibition of Posterior Capsule Opacification by a Capsular Adhesion–Preventing Ring

Author Affiliations

Author Affiliations: Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan.

Arch Ophthalmol. 2009;127(4):471-474. doi:10.1001/archophthalmol.2009.63
Abstract

Objective  To assess the inhibitory effect of a capsular adhesion–preventing ring (CAPR) that facilitates aqueous humor circulation into the capsular bag on posterior capsule opacification (PCO) formation after cataract surgery.

Methods  After phacoemulsification, a polymethyl methacrylate intraocular lens with (n = 5) or without (n = 5) a CAPR was implanted in rabbit eyes. The inhibitory effect of the CAPR on PCO formation was assessed by stereoscopic microscopy and histologic examination 8 weeks after surgery.

Results  All eyes in which a CAPR was implanted demonstrated remarkably less PCO than the control eyes. Neither anteroposterior capsular adhesion nor regeneration of lens fiber occurred in 2 eyes in the CAPR group. The remaining 3 eyes with a CAPR showed partial capsular adhesion and limited lens fiber regeneration in the resultant closed capsular space.

Conclusions  The CAPR appears to prevent PCO formation by separating the anterior and posterior capsules and allowing circulation of aqueous humor, including growth inhibitory factors, into the equatorial space of the capsule through the holes and grooves in the ring.

Clinical Relevance  A CAPR may be useful for preventing PCO in the clinical setting.

Posterior capsule opacification (PCO), a major unsolved postoperative complication of cataract surgery, develops during the process of wound healing and regeneration of the crystalline lens. It occurs as a result of migration, proliferation, and transdifferentiation of lens epithelial cells (LECs). Therefore, preventing these cellular events should inhibit PCO formation.

The existence of putative growth inhibitory factors in aqueous humor (AH) has been speculated to explain why there is little proliferation of corneal endothelial cells in vivo.1 We have reported that a 10% solution of human AH inhibits proliferation of cultured bovine LECs, and this inhibition is blocked by the addition of anti–transforming growth factor β2 (TGF-β2) neutralizing antibody, suggesting a cell growth–inhibitory effect of TGF-β2 in AH.2 Although AH in the early postoperative period of cataract surgery is rich in serum proteins,3 including growth factors that promote LEC proliferation,4,5 restoration of the blood-aqueous barrier normalizes AH composition with time. We hypothesized that free access of normal AH containing growth inhibitory factors to the LECs could prevent LEC proliferation and subsequent PCO formation. We developed a capsular adhesion–preventing ring (CAPR) that allows AH circulation within the capsular bag and examined its inhibitory effect on the formation of PCO in rabbit eyes.

METHODS
THE CAPR

The acrylic CAPR (Lenstec Co Ltd, St Petersburg, Florida) has 4 grooves for intraocular lens (IOL) loop fixation and 4 holes for AH circulation within the capsular bag. A 4-groove design was used because it would reduce dialing of the IOL loop and add AH circulation through the remaining 2 grooves. The inner and outer diameters of the CAPR are 6.5 and 8.5 mm, respectively, with a 2.0-mm height (Figure 1A). The CAPR pushes the anterior capsule away from the posterior capsule, thereby preventing anteroposterior capsular adhesion and allowing AH circulation into the capsular bag through the grooves and holes (Figure 1B).

SURGICAL PROCEDURES

Because interindividual differences in biological reaction of wound healing affect the extent of PCO formation, we decided to compare the protective effects of the CAPR in the same individuals by performing bilateral surgical procedures with and without the CAPR. All animal experiments were conducted with particular attention to visual consequences, and postoperative behavioral abnormality was carefully monitored daily. Young Dutch pigmented rabbits (n = 5), weighing 1.9 to 2.3 kg (mean, 2.13 kg), were used in this study. After the animals were anesthetized with a combination of intravenous pentobarbital sodium and intraperitoneal thiamylal sodium, a 3.0-mm sclerocorneal incision was made. A small continuous curvilinear capsulorrhexis (3 to 4 mm in diameter) was created and then phacoemulsification and aspiration were performed. The continuous curvilinear capsulorrhexis should be smaller than 5 mm in diameter because the CAPR needs to be covered completely by the anterior capsule to keep the anterior and posterior capsules separated. After enlargement of the sclerocorneal incision to 5.5 mm, in-the-bag insertion of the CAPR followed by implantation of a polymethyl methacrylate IOL (model C455F, +20.0 diopters; Optical Radiation Corporation, Azusa, California) was conducted in 5 eyes. The IOL loops were fixated in the grooves of the CAPR by a dialing technique. As a control, a polymethyl methacrylate IOL without the CAPR was implanted in the 5 fellow eyes. After the surgery, antibiotic (ofloxacin) and anti-inflammatory (betamethasone sodium phosphate and diclofenac sodium) eye drops, as well as atropine sulfate and tropicamide, were given twice a day for 1 week.

ASSESSMENT OF PCO

The effects of the CAPR on PCO formation were examined 8 weeks after surgery by a single investigator (T.N.) in an unmasked fashion owing to the readily noticeable CAPR in the samples, which is a potential limitation of the study. We chose the examination timing of 8 weeks after surgery on the basis of a previous report by Legler et al6 in which a similar experimental design was used. Animals were killed by intravenous administration of a lethal dose of pentobarbital sodium. The eyeballs were enucleated before the corneas and posterior halves of the eyes were removed to isolate the anterior halves. These anterior segments were fixed in 10% neutral buffered formalin for 1 week and then embedded in a plastic (Technovit 7100; Heraeus Kulzer GmbH, Wehrheim, Germany). Six-micrometer sections were stained with toluidine blue before histologic observation by light microscopy. The degree of PCO was scored according to the following scales: adhesion of anterior capsule to posterior capsule, 0 (none), 1 (a little), 2 (less than half circle), 3 (more than half but not entire circle), or 4 (entire circle); regeneration of lens fiber in the capsular bag, 0 (none), 1 (a little), 2 (less than half circle), 3 (more than half but not entire circle), or 4 (entire circle); fibrosis of posterior capsule under the IOL optic, 0 (none), 1 (mild), 2 (moderate), or 3 (severe); and wrinkles in the posterior capsule, 0 (none), 1 (mild), 2 (moderate), or 3 (severe). The first 3 measures were determined by stereoscopic microscopy before sample fixation. Posterior capsule wrinkles were assessed by light microscopy. The mean scores between groups were statistically compared by means of the Mann-Whitney test.

RESULTS

Markedly fewer PCOs developed in the eyes implanted with the CAPR than in the control eyes; 2 eyes (40%) in the CAPR group had no PCO. The mean scores for all PCO measures were significantly less in the CAPR group than in the control group (Table).

Histologic photographs are shown in Figure 2. In control eyes (Figure 2, right panels), the obvious anteroposterior capsular adhesion around the capsulotomy margin and lens fiber regeneration, resulting in thick PCO formation, were observed throughout the capsular bag. On the contrary, PCO measures in the CAPR group (Figure 2, left panels) were absent or minute. Strikingly, neither anteroposterior capsular adhesion nor regeneration of lens fiber occurred in 2 eyes in the CAPR group (Figure 2A and B). An anteroposterior capsular adhesion peripheral to the CAPR appeared in 2 eyes, causing lens fiber regeneration in those closed spaces (Figure 2C and D). Only 1 eye in the CAPR group showed massive regeneration of lens fiber invading beneath the IOL optic, although the center of posterior capsule was still clear (Figure 2E).

COMMENT

Our results demonstrated that formation of PCO was reduced when anteroposterior capsular separation and AH circulation into the capsular bag were successfully obtained by the CAPR. Partial anteroposterior capsular adhesion, resulting in limited AH circulation, caused regeneration of lens fiber in the closed capsular space (Figure 2C and D). Because the number of experimental eyes was not large, it would be difficult to draw firm conclusions from our results. However, there was substantially less regeneration of lens fiber in the CAPR group, except in the 1 eye shown in Figure 2E. Therefore, CAPR should have considerable utility in reducing PCO formation.

These results lead to the question: Is the separation itself sufficient to prevent PCO formation, or are both separation and AH circulation necessary? To answer this question, experiments using a holeless and grooveless CAPR should be performed. At least 2 grooves are necessary to support the IOL loops, allowing AH circulation into the equatorial space, although the amount of circulating AH would be substantially reduced. Therefore, whether separation itself or both of these factors contributed to the inhibition of PCO was not proved in our study. Although comparison of PCO formation between eyes having a CAPR with holes and eyes having a CAPR with no holes would be a better design to avoid the effects of this bulky additional implant on LEC behavior, our experimental design would still be acceptable.

Overall, the following lines of evidence suggest the potential role of AH in preventing PCO formation. Regeneration of lens fiber reportedly never starts before the postoperative anteroposterior capsular adhesion in rabbits,7 suggesting that direct contact of AH with LECs prevents PCO formation. Accordingly, the existence of factors inhibiting proliferation of LECs in the AH was speculated. Although AH at the early postoperative period stimulates proliferation of LECs,4,5 the growth-promoting effect of postoperative AH is gradually decreased and disappeared at around 1 month after the surgery.4 Previous reports by our group2 and others1 indicated that TGF-β2 in the normal AH inhibits proliferation of LECs and corneal endothelial cells. This would be explained by the findings that TGF-β2 induces apoptosis of LECs and increases numbers of pyknotic nuclei.8 In clinical cases, LEC outgrowth from the margin of the anterior capsulotomy onto the surface of the IOL optic is common.911 Although this LEC proliferation continues for 1 month postoperatively, it gradually regresses and the IOL surface becomes clear.911 A similar phenomenon has been reproduced in rabbit experiments.12 Again, it is conceivable that postoperative AH contains growth-promoting factors and normal AH does have growth inhibitory factors, such as TGF-β2. Therefore, we believe that, in addition to separating the anterior and posterior capsules, circulation of AH with growth-inhibitory factors into the equatorial space of the capsule would be required for reduction of PCO formation.

From a clinical point of view, CAPR might be a beneficial device in addition to bag-in-the-lens IOL13,14 in cataract surgery for children where PCO formation is a major impediment to the use of IOLs. Because implantation of bag-in-the-lens IOLs is technically difficult, CAPR might become another choice for pediatric cataract surgery with IOL implantation.

In conclusion, the use of the CAPR can inhibit PCO formation in rabbit eyes when anteroposterior capsular separation and AH circulation into the capsular bag are obtained. The CAPR may be useful for PCO prevention in humans as well.

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Article Information

Correspondence: Toshiyuki Nagamoto, MD, Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan (nagamoto@nagamoto.org).

Submitted for Publication: July 10, 2008; final revision received November 3, 2008; accepted December 2, 2008.

Author Contributions: Dr Nagamoto had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: Dr Nagamoto has the US patent (US Patent No. 6063118) and has applied for the Japanese patent (Patent Application No. 9-369267) for the CAPR and has no financial contract with any company.

References
1.
Chen  KHHarris  DLJoyce  NC TGF-β2 in aqueous humor suppresses S-phase entry in cultured corneal endothelial cells. Invest Ophthalmol Vis Sci 1999;40 (11) 2513- 2519
PubMed
2.
Kurosaka  DNagamoto  T Inhibitory effect of TGF-β2 in human aqueous humor on bovine lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 1994;35 (9) 3408- 3412
PubMed
3.
Weinsieder  ABriggs  RReddan  JRothstein  HWilson  DHarding  CV Induction of mitosis in ocular tissue by chemotoxic agents. Exp Eye Res 1975;20 (1) 33- 44
PubMedArticle
4.
Wallentin  NWickström  KLundberg  C Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 1998;39 (8) 1410- 1418
PubMed
5.
Reddan  JRWeinsieder  AWilson  D Aqueous humor from traumatized eyes triggers cell division in the epithelia of cultured lenses. Exp Eye Res 1979;28 (3) 267- 276
PubMedArticle
6.
Legler  UFApple  DJAssia  EIBluestein  ECCastaneda  VEMowbray  SL Inhibition of posterior capsule opacification: the effect of colchicines in a sustained drug delivery system. J Cataract Refract Surg 1993;19 (4) 462- 470
PubMedArticle
7.
Blomstedt  GFagerholm  PGallo  JPhilipson  B After-cataract in the rabbit eye following extracapsular cataract extraction: a wound healing reaction. Acta Ophthalmol Suppl 1987;18293- 99
PubMed
8.
Maruno  KALovicu  FJChamberlain  CG McAvoy  JW Apoptosis is a feature of TGF bet–induced cataract. Clin Exp Optom 2002;85 (2) 76- 82
PubMedArticle
9.
Nagamoto  THara  E Postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. J Cataract Refract Surg 1995;21 (2) 208- 211
PubMedArticle
10.
Ibaraki  NOhara  KMiyamoto  T Membranous outgrowth suggesting lens epithelial cell proliferation in pseudophakic eyes. Am J Ophthalmol 1995;119 (6) 706- 711
PubMed
11.
Kurosaka  DKato  K Membranous proliferation of lens epithelial cells on acrylic, silicone, and poly(methyl methacrylate) lenses. J Cataract Refract Surg 2001;27 (10) 1591- 1595
PubMedArticle
12.
Saika  SOhmi  SKanagawa  R  et al.  Lens epithelial cell outgrowth and matrix formation on intraocular lenses in rabbit eyes. J Cataract Refract Surg 1996;22 ((suppl 1)) 835- 840
PubMedArticle
13.
De Groot  VLeysen  INeuhann  TGobin  LTassignon  MJ One-year follow-up of bag-in-the-lens intraocular lens implantation in 60 eyes. J Cataract Refract Surg 2006;32 (10) 1632- 1637
PubMedArticle
14.
Tassignon  MJDe Veuster  IGodts  DKosec  DVan den Dooren  KGobin  L Bag-in-the-lens intraocular lens implantation in the pediatric eye. J Cataract Refract Surg 2007;33 (4) 611- 617
PubMedArticle
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