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Laboratory science

Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges

Nishi, Okihiro MDa,*; Nishi, Kayo MDa; Wickström, Kerstin PhDb

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Journal of Cataract & Refractive Surgery: October 2000 - Volume 26 - Issue 10 - p 1543-1549
doi: 10.1016/S0886-3350(00)00426-0
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Abstract

The incidence of posterior capsule opacification (PCO) in eyes with an AcrySof® intraocular lens (IOL) is reportedly significantly lower than in those receiving a poly(methyl methacrylate) (PMMA) IOL.1,2 We previously reported that an AcrySof IOL with sharp optic edges significantly inhibits migration of lens epithelial cells (LECs) onto the posterior capsule in rabbit eyes compared to a PMMA IOL with rounded edges.3 Because acrylic IOLs are 3 times as adhesive to collagen film as PMMA IOLs,4,5 the question becomes: Which factor—IOL design or material composition—has a greater influence on PCO?

Further studies found that a PMMA IOL with sharp rectangular optic edges identical in design to AcrySof IOL edges also significantly inhibits PCO.6 The migration of LECs with both IOL types was inhibited at the sharp rectangular bend in the capsule created by the sharp optic edges. We concluded that the discontinuous capsular bend created by this optic edge inhibits LEC migration.

The rationale for this conclusion is based on our in vitro cell culture observations.6 During culture, LECs ceased to proliferate when they reached the rectangular well wall. This is known as a confluent culture. However, along the wall of U-shaped wells, LECs grew and ascended. The PMMA IOL with sharp rectangular optic edges was made specifically for use in that study. In this current study, we compared a commercially available silicone IOL with sharp rectangular optic edges (CeeOn 911) with the AcrySof IOL in terms of PCO prevention.

Materials and Methods

Intraocular Lens and Surgery

The 3-piece silicone CeeOn 911 IOL (Pharmacia & Upjohn) has an optic edge that is sharp, rectangular, and similar to that of the AcrySof IOL (Figure 1). The CeeOn's optic is thicker and the edge profile thinner because of the lower refractive index of the lens' material composition.

Figure 1.
Figure 1.:
(Nishi) Optic edge design of the CeeOn 911 (above) and AcrySof (below) IOLs. Note the sharp optic edge on both IOLs and that the CeeOn 911 optic is slightly thicker because of its lower refractive index.

A CeeOn 911 was implanted in 1 eye and an AcrySof IOL in the contralateral eye in 7 rabbits after phacoemulsification. The surgery was performed so that the entire anterior capsule margin was completely apposed to the IOL optic.

Postoperative Examinations

The bending effect (ie, creation of a sharp capsular bend by the optic edge), LEC migration onto the posterior capsule, PCO evaluated by Miyake–Apple view, and histopathology of the lens capsule were evaluated 3 to 4 weeks after surgery.

The histopathological preparation was performed as previously reported.6 All sections were stained with hematoxylin & eosin except those of rabbit 3, which were stained with toluidine blue.

The capsular bend effect was evaluated using 4 grades: no effect (–), detectable (+), obvious (++), and distinct (+++). The grade was determined according to how distinctly the capsular bend was created by the optic edge and the amount of LECs that migrated over the optic edge further toward the posterior capsule.

Overall PCO was evaluated by estimating the cleanliness of each of the 4 quadrants of the entire posterior capsule area within the IOL optic as follows: none (–), slight (+), obvious (++), and distinct (+++). Slight (+) was assigned when the iris pattern was still detectable. Obvious (++) was assigned when the iris pattern was hardly detectable. Distinct (+++) was assigned when the iris pattern was not detectable.

Results

One rabbit was omitted from evaluation because the capsulorhexis edge was torn. The opening eventually became so eccentric that the capsular margin was not completely in apposition to the IOL optic.

Miyake–Apple View

A vast Soemmering's ring cataract was formed in the capsules of both eyes in all rabbits, showing that the migrating LECs were inhibited at the optic edge except in rabbit 4.

In rabbits 1 and 2, capsular bending was obvious along the posterior optic edge. In both eyes of rabbits 3 and 4 and in the eye that received a CeeOn 911 in rabbit 5, the bend effect was diminished at a part of the optic circumference; some migrating LECs were observed at those sites. In rabbit 6, the edge bend was destroyed by the formation of a vast Soemmering's ring; abundant LECs migrated onto the posterior capsule; the central part of the posterior capsule appeared clear (ie, free from migrating LECs).

The posterior capsule was clearer with the CeeOn in rabbit 2, rabbit 3 (Figure 2), and rabbit 6. It was clearer with the AcrySof in rabbit 1, rabbit 4 (Figure 3), and rabbit 5. The central posterior capsule appeared to be clear in most eyes.

Figure 2.
Figure 2.:
(Nishi) Lens capsules containing a CeeOn 911 IOL (left) and an AcrySof IOL (right) on Miyake–Apple view. The posterior capsule appears clearer in the eye with the CeeOn IOL (rabbit 3).
Figure 3.
Figure 3.:
(Nishi) Lens capsules of rabbit 4; Miyake–Apple view. More PCO formed in the eye with the CeeOn IOL (left) than in the eye with the AcrySof (right) IOL.

Histopathological Findings

The capsular bend effect and its prevention of migrating LECs was observed in most eyes. In rabbits 3, 4, and 5, the capsular bend and preventative effect were slightly greater in the eye with the AcrySof IOL (Figure 4). In these eyes, some migrating LECs were seen on the posterior capsule in the CeeOn group, although the overall PCO on Miyake view was less in the eye with the CeeOn in rabbit 3. In rabbit 1, the bend effect was present and similar, but there was more PCO in the eye with the CeeOn. In rabbit 2 (Figure 4), the bend effect was similar with both IOLs, but PCO was slightly less in the eye with the CeeOn (Miyake view). Once the capsular bend was diminished or abolished by a vast Soemmering's ring cataract, an abundance of LECs migrated onto the posterior capsule (rabbit 6) (Figure 5).

Figure 4.
Figure 4.:
(Nishi) Histopathological findings of the lens capsule of rabbit 2. The lens capsule is wrapped tightly around the optic, causing a distinct bend in the capsule of both IOLs. At that site, LEC migration was inhibited. The edge and PCO preventative effects were similar between the IOLs.
Figure 5.
Figure 5.:
(Nishi) Histopathological findings of rabbit 6. A vast Soemmering's ring cataract annulled the capsular bend, allowing abundant LEC migration onto the posterior capsule in both eyes.

Eyes with AcrySof IOLs seemed to have an increased amount of differentiated myofibroblast-like cells. In eyes with CeeOn IOLs, LEC morphology remained epithelial (Figure 6).

Figure 6.
Figure 6.:
(Nishi) Histopathological findings of LECs that migrated onto the posterior capsule. Left: Epithelioid cells are evenly spread on the posterior capsule in the CeeOn IOL eye of rabbit 5. Occasional cells are elongated, suggesting a state toward lens fiber differentiation. Right: Several plaque formations, 50 to 500 μm in length, are seen. Between these formations, the capsule is clear. The plaques consist of myofibroblast-like contractile cells with elongated nuclei that wrinkle the posterior capsule (PC = posterior capsule).

Summary of Results

Table 1 gives a detailed summary of the results. The evaluations were based on the Miyake–Apple view and histological findings because histology was performed on 1 sectional level only. In brief, in rabbit 1, there was no difference in the capsular bend effect, but the eye with the AcrySof IOL had slightly less PCO. In rabbit 2, there was no difference in the bend effect, but the eye with the CeeOn 911 had less PCO. In rabbit 3, the eye with the AcrySof showed a better capsular bend effect, but the eye with the CeeOn had less PCO. In rabbit 4, the eye with AcrySof showed a better bend effect and had slightly less PCO. In rabbit 5, the eye with the AcrySof showed a better bend effect and had less PCO. In rabbit 6, the bend effect was lost because of thick PCO in both eyes, but PCO formation was less in the eye with the CeeOn.

Table 1
Table 1:
Comparison of the prevention of PCO: CeeOn 911 versus AcrySof.

Discussion

AcrySof showed a better capsular bend effect in the histological sections. This effect may have been caused by the adhesiveness of the acrylic material and the thinner optic, which created a sharper edge because of the AcrySof's higher refractive index. These factors may enhance the creation of a sharper capsular bend. However, the Miyake—Apple view showed that overall, there was no apparent difference in PCO development between the 2 IOLs, particularly in the central pupillary area, at least until 3 to 4 weeks after surgery. Thus, the silicone CeeOn 911 IOL with sharp rectangular optic edges showed a PCO prevention effect similar to that of the AcrySof IOL.

These results and those of previous studies using a PMMA IOL with sharp optic edges6 suggest that an IOL design with sharp rectangular optic edges prevents PCO regardless of the IOL's material composition (acrylic, PMMA, or silicone) and that the preventive effect of an AcrySof IOL on PCO may be ascribed mainly to its sharp rectangular optic design. We think that the capsular bend created by the sharp optic edge may induce contact inhibition of the migrating LEC.

However, an AcrySof IOL is 3 times as adhesive to collagen membrane as the CeeOn4,5; this adhesiveness may retard LEC migration. Or, the strong adhesion between the IOL and posterior capsule may shut out LECs, preventing them from migrating onto the posterior capsule. How and to what extent the adhesiveness (ie, material composition) affects LECs must be clarified by a comparative study between an acrylic IOL with rounded edges and an AcrySof IOL. We are currently conducting such a study.

Implantation of the AcrySof IOL seemed to increase the amount of differentiated myofibroblast-like cells and plaque formation, whereas more epithelial cells were evenly spread throughout the posterior capsule with the CeeOn IOL. Whether this difference was caused by material composition or mechanically by the better edge effect and stronger adhesion between the IOL and posterior capsule must be clarified. Another issue is which cell type will eventually result in a clinically more significant decrease in visual acuity.

Creation of a sharp bend in the capsule depends not only on optic design but also on IOL material and surgical technique. Creating a well-centered continuous curvilinear capsulorhexis (CCC) smaller than the IOL optic is crucial as it ensures that the entire circumference of the capsular edge is in apposition to the IOL optic. Because IOL design, material composition, and surgical technique are the 3 main factors influencing PCO, 2 of the factors should be matched in a comparative clinical study of PCO between 2 IOLs. This will make the data obtained in future studies more accurate, reliable, and comparable.

The preventive effect of an IOL on PCO has been explained by various concepts such as capsular stretching, compression, the barrier effect, and no space, no cells theory. Thus, the effect of posterior convexity of a single-piece IOL or the sharp edge of a plano-convex IOL, Hoffer ridge IOL, and meniscus ridge IOL7 should be a result of these concepts. However, these IOLs may help create a firm capsular bend or angle at the optic edge rather than providing compression or no space. The conflicting results8 obtained with this barrier edge or ridge may be caused by different surgical techniques and the anatomy of the individual anterior segment. In particular, apposition of the anterior capsule edge on the optic is a prerequisite of creating an appropriate capsular bend. Because these IOLs were mainly used before the advent and widespread adoption of CCC, which allows secure in-the-bag IOL fixation, we wonder whether a meniscus-edge or ridge IOL would reduce the incidence of PCO if these lenses were reintroduced.

Two studies in the mid-1990s found significantly lower degrees of PCO with a plano-convex PMMA IOL (posterior plano with sharp edges).9,10 The authors believe that the sharp optic edge exerts greater compression on the posterior capsule and acts as a barrier to LEC migration. However, it is possible that the sharp posterior optic edge creates a sharp bend in the capsule, which induces contact inhibition of migrating LECs, as shown in a study with the AcrySof IOL. Ursell et al.2 report that the lower PCO incidence achieved with the AcrySof IOL may be material dependent and is unlikely to be design dependent. In their study, 90 eyes were prospectively randomized to receive a PMMA, silicone, or AcrySof IOL. Posterior capsule opacification was assessed by a digital illumination camera using a dedicated software program. Because the designs of the 3 IOLs were different, there were 2 variables in the study: material and design. Hollick et al.11 found considerably less PCO with AcrySof than with silicone IOLs. The silicone lens had a lower refractive index, and the design was different among the 3 types of IOL. Thus, there were also 2 variables in that study.

In conclusion the silicone CeeOn 911 IOL showed a PCO preventive effect similar to that of the AcrySof IOL in an animal study. These results, and those of a previous comparative study between PMMA and AcrySof IOLs, show that the sharp, rectangular optic edge significantly inhibits migrating LECs regardless of the IOL's material composition, which appears to be the most important factor in preventing PCO. The AcrySof's preventative effect may be mainly the result of its sharp rectangular optic edge. However, how and to what extent the material composition (adhesiveness) plays a role need further study. In future comparative clinical studies on PCO rates between 2 IOLs, the lens' design or material composition should be the same.

References

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© 2000 by Lippincott Williams & Wilkins, Inc.