Since the release of the first square-edged IOL, the AcrySof MA60BM IOL (Alcon Laboratories, Inc., Fort Worth, TX), in 1995, several studies have evaluated the lens' ability to maintain a clear posterior capsule. Not until the existence of the square edge to reduce PCO did we need the term dysphotopsias to describe the unwanted images this edge design creates. A more complete understanding of this mechanism allows us to generate better designs that reduce PCO without producing unwanted images, and some advanced optic designs are already available (Figure 1).1 The confounding question regarding the square edge is why exactly it prevents PCO.
CORRELATIONS TO THE YAG
David Apple, MD, of Salt Lake City assessed the square-edged MA60BM via the highly objective Miyake-Apple views of cadaver specimens.2 The overall YAG rate for this IOL increased from 0.9% in January 2000 to 3.3% in January 2001. Abundant cortical regeneration in the form of Soemmering's ring, indicative of poor cortical cleanup, was the primary factor correlated with YAG capsulotomy. There was also a strong correlation of capsulotomy with failure of in-the-bag fixation, but it did not reach statistical significance. In addition, overlapping of the optic by the continuous tear capsulotomy had a preventative effect on PCO, with greater overlapping providing more protection.
Dr. Apple's work demonstrates the surgeon's ability to manipulate the likelihood of PCO independent of the IOL's design, a finding that should motivate surgeons to improve current surgical techniques. Full cortical removal may not seem important for the completion of a given case, but decreasing the residual cortex for an individual patient will lessen the burden of regenerating cortex in the future. The weakness of the cadaver study is identifying a true YAG rate for a given IOL at a specific elapsed time. Although millions of patients have received AcrySof MA60BM lenses worldwide, only 349 IOLs were available for this evaluation. None of the specimens contained the critical data of time elapsed from surgery before YAG or obtaining of the specimen.
THEORIES ON PCO PREVENTIONContact Inhibition of Lens Epithelial Cells
The concept of a square-edged IOL's preventing PCO by inhibiting the migration of lens epithelial cells (LECs) was first proposed by Okihiro Nishi, MD, and Kayo Nishi, MD, both of Osaka, Japan, in a breakthrough 1999 article.3 Their study compared a sharp-edged PMMA IOL to the AcrySof MA60BM lens in a rabbit-eye model. As expected, prominent Soemmering's ring formation developed in both sets of eyes. Both posterior capsules of both sets appeared completely clear, a finding that identified the edge and not the lens material as the significant factor.
Dr. Okihiro Nishi observed that a distinct change in the posterior capsule's configuration occurred against the square edge of the IOL, which he termed the capsular bend. The capsule showed “complex frills, pleats or gatherings” peripheral to the IOL and extending from the optic's edge to the equator. The configuration at the optic's edge, however, demonstrated a “distinctly discontinuous, sharp square bend” with tight wrapping around the posterior optic. Dr. Nishi proposed that this sharp angle of contact effectively inhibited the migration of LECs onto the posterior capsule and thereby kept the space optically clear.
Pressure Profile
In 2002, David Spaulton, FRCSC, and his group published two articles proposing an alternative explanation for the square-edge effect. In the first article, Gurpreet Bhermi, FRCOphth, described the results of LEC growth in vitro.4 The investigators were unable to identify a contact inhibition created by a square-edged PMMA culture block in preventing LEC growth and migration. The culture block's square edge, however, did significantly slow cellular migration compared with a round-edged culture block, a finding that can be attributed to the greater distance traversed by the cells migrating around the square edge. The investigators acknowledged that this does not prove that contact inhibition does not exist in vivo, but that contact inhibition is not the only effect of the square edge.
The second article mathematically modeled the pressure effect of a square-edged IOL versus a round-edged IOL.5 The researchers reported a 69% increase in the pressure exerted on the posterior capsule at the point of contact by a square edge compared with a round edge. This calculated force against the capsule drops considerably behind the optic once the LECs have reached the lens' edge, and the posterior haptic angulation enhanced the pressure effect. The authors surmised that this pressure effect was the main effect of the square edge and is enhanced by posterior haptic angulation.
Responses to the Studies
The fundamental differences between these two theories were best summarized in the Letters section of the June 2003 issue of the Journal of Cataract and Refractive Surgery.6 In response to Dr. Bhermi's article, Dr. Nishi vigorously defended contact inhibition as the mechanism of PCO prevention in capsular bend formation when associated with a square optic edge. He presented an illustration of multilayering cells in a rabbit-eye specimen in which the cells did not climb the posterior capsule. In a personal e-mail message, Dr. Nishi identified that the vertical mirror image of the illustrated effect appeared in the superior aspect of the capsule, which, surprisingly, suggested that this phenomenon is independent of gravity.
Dr. Spaulton's response cited examples of the square edge's failure to inhibit PCO effectively, a point on which I elaborate later in this article. He also noted that some IOLs form an effective capsular bend to inhibit PCO without the square edge, such as the round-edged, second-generation, silicone SI-40 NB lens (Advanced Medical Optics, Inc., Santa Ana, CA). Dr. Spaulton's letter did not so much refute the role of bend formation in inhibiting PCO as it identified the multifactorial nature of the process. He did not, however, agree that contact inhibition alone can account for the PCO-preventing effect of the square optic edge.
How well does laboratory study correlate to clinical experience? Dr. Spaulton's work involved coating the culture wells with collagen. After cataract surgery, collagen is immediately present as a constituent of the capsule, but its presence on the IOL surface in vitro is uncertain for several days.7 It is likely that the collagen created an artificial scaffold for cellular migration and defeated any potential inhibition from the hydrophobic chemical properties of the PMMA culture well. Similarly, the open nature of a culture well is unlike the tight space between the anterior and posterior capsules at the optic's edge.
Speed of Capsular Bend Formation
The two mechanisms of contact inhibition versus point pressure on the capsule are not entirely discordant when time is factored into the equation. Using daily evaluation with Scheimpflug videophotography, researchers compared the speed of complete contact of the anterior and posterior capsules with the IOL for the silicone SI-40 NB and hydrophobic acrylic MA60BM lenses.8 Both IOLs have 10º angulated haptics, 6.0-mm optics, and demonstrated abilities at PCO prevention. The researchers found that complete capsular contact for the SI-40 NB was much faster (<8 days vs 11 days) than for the MA60BM lens.
Dr. Nishi and his colleagues had already published similar work describing the capsular bending index.9 Their work focused on the wrapping of the posterior capsule around the edge of the optic as it fused to the anterior capsule. They found that the SI-40NB induced the fastest capsular bend, followed by the three-piece AcrySof MA60BM lens, and the UV26T PMMA lens (Menicon, Nagoya, Japan) at a distant third. At 1 year, all examined eyes had a complete capsular bend, regardless of lens material. Given the inability of PMMA to prevent PCO despite similar bending properties, Dr. Nishi concluded that the faster capsular bending index with the silicone and hydrophobic acrylic IOLs effectively prevented PCO by inhibiting LEC migration.
DEFEATING THE SQUARE EDGE
Failure of the square optic edge also significantly improves our understanding of how this design reduces PCO. Two factors appear to have a profoundly deleterious effect on a square optic edge's ability to prevent PCO. The first involves using hydrophilic acrylic material for the optic. Because the ease of cellular proliferation onto the surface of this lens material has been well documented, the pertinent question was whether the square-edged optic of this material would inhibit PCO as effectively as one made of either second-generation silicone or hydrophobic acrylic. Catherine Heatley, MD, presented a comparison of the PCO performance of two single-piece acrylic IOLs.10 She had implanted the square-edged hydrophilic Centerflex (Rayner Optical Company, Brighton, England) in one eye of subjects and an AcrySof SA60AT in their other eye. At all time intervals up to 1 year, the Centerflex showed greater PCO than the AcrySof, averaging greater than 35% compared with less than 10%, respectively. Dr. Heatley concluded that the hydrophilic material was the most likely cause of this considerable difference.
The second contributing factor in defeating the square edge is the inhibition of capsular fusion, which blocks capsular bend formation. Dr. Nishi demonstrated a reduced capsular bend formation in a rabbit-eye study for both a 5.5-mm single-piece AcrySof lens and an experimental 7.0-mm AcrySof lens when compared with a three-piece AcrySof IOL.11 He found that the haptics prevented capsular fusion due to their bulk and permitted abundant LEC migration into the space near the edge of the optic. He also proposed that LEC proliferation disturbed capsular fusion by creating potential space at the junction between the haptic and bulky optic.
Considering its hydrophobic acrylic material and square edge, it is not surprising that repeated 1-year results show good PCO inhibition by the SA60AT. Clinically, however, the optic-haptic junction of this IOL is its greatest weakness at long-term PCO reduction, and virtually no barrier exists at this point to the spreading of regenerating cortical material onto the posterior capsule (Figures 2 and 3). The relatively rapid occurrence of PCO in this patient in whom I implanted a SA60AT IOL could be due either to the failure of the capsular bend to form and inhibit cellular proliferation or to a lack of pressure in this region by a square edge against the capsule due to the lack of haptic compression. Unfortunately, the design failure of the SA60AT does not allow us to fully distinguish between these two potential mechanisms.
CONCLUSION
Short-term prevention of PCO becomes a race between the formation of the capsular bend and the speed of cell migration. Capsular adhesion depends upon several factors. Mechanically, they include thorough cortical cleanup and complete capsulorhexis coverage. Physiologically, LECs become activated to seal the capsule to the IOL by inflammation due to the direct trauma of surgery, circulating factors from the breakdown of the blood-aqueous barrier, and stimulation from the IOL material itself. Understanding the absolute effect of the square edge entails answering which of the following occurs first: (1) the pressure of the square edge to sequester the space behind the optic or (2) the fusion of the anterior and posterior capsules at the edge of the optic to create the situation necessary for contact inhibition to occur.
Clearly, all of these factors work in concordance immediately after cataract surgery. The design of the lens optic should include posterior angulation of the haptics to maximize pressure against the capsule such that the greatest indentation force is generated at the square edge. This design keeps the capsule tight against the posterior optic surface and increases the distance that migrating LECs must travel to reach the posterior optic space. The material of the optic will then induce rapid contact of the anterior and posterior capsular leaflets, an action followed by fusion as fibrosis leads to a discontinuous capsular bend at the edge of the optic. This quickly formed tight space effectively inhibits the further proliferation of the LECs, the normal existence of which is a monolayer at the capsular periphery.
Steven H. Dewey, MD, practices in Colorado Springs, Colorado, with the Colorado Springs Health Partners. He is a consultant for Advanced Medical Optics, Inc. Dr. Dewey may be reached at (719) 475-7700; sdewey@cshp.net.1. Buehl W, Findl O, Menapace R, et al. Effect of an acrylic intraocular lens with a sharp posterior optic edge on posterior opacification. J Cataract Refract Surg. 2002;28:1105-1111.
2. Schmidbauer JM, Vargas LG, Apple DJ, et al. Evaluation of neodymium:yttrium-aluminum-garnet capsulotomies in eyes implanted with Acrysof intraocular lenses. Ophthalmology. 2002;109:1421-1426.
3. Nishi O, Nishi K. Preventing posterior capsule opacification by creating a discontinuous sharp bend in the capsule. J Cataract Refract Surg. 1999;25:521-526.
4. Bhermi GS, Spalton DJ, El-Osta AA, Marshall J. Failure of a discontinuous bend to prevent lens epithelial cell migration in vitro. J Cataract Refract Surg. 2002;28:1256-1261.
5. Boyce JF, Bhermi GS, Spalton DJ, El-Osta AR. Mathematical modeling of the forces between an intraocular lens and the capsule. J Cataract Refract Surg. 2002;28:1853-1859.
6. Linnola RJ, Sund M, Ylonen R, Pihlajaniemi T. Adhesion of soluble fibronectin, vitronectin, and collagen type IV to intraocular lens materials. J Cataract Refract Surg. 2003;29:146-152.
7. Nishi O. Effect of a discontinuous capsule bend. J Cataract Refract Surg. 2003;29:1051-1052, author reply 1052.
8. Hayashi H, Hayashi K, Nakao F, Hayashi F. Elapsed time for capsular apposition to intraocular lens after cataract surgery. Ophthalmology. 2002;109:1427-1431.
9. Nishi O, Nishi K, Akura J. Speed of capsular bend formation at the optic edge of the acrylic, silicone, and poly(methyl methacrylate) lenses. J Cataract Refract Surg. 2002;28:431-437.
10. Heatley C. Comparison of PCO with Hydrophilic and Hydrophobic Single-Piece Acrylic IOL. Paper presented at: ASCRS/ASOA Symposium on Cataract, IOL and Refractive Surgery; June 2003; San Francisco, CA.
11. Nishi O, Nishi K. Effect of the optic size of a single-piece acrylic intraocular lens on a posterior capsule opacification. J Cataract Refract Surg. 2002;28:1236-1240.
