Posterior capsule opacification (PCO) is undeniably the most common complication of otherwise uncomplicated cataract surgery. Nd:YAG laser capsulotomy is the simplest intraocular surgical procedure we perform as ophthalmologists, but at what cost? For the patient, the clouding of the posterior capsule leads to significant morbidity as they are unable to fully distinguish the cause of their failing vision from other more ominous problems such as macular degeneration. For society, Nd:YAG laser capsulotomy is the second-most frequently performed procedure for Medicare beneficiaries, and at a cost of more than $250 million each year.
With rates of PCO approaching 50% for some IOL designs and surgical techniques, most ophthalmologists have thought of YAG capsulotomy as inevitable. The weight of evidence has now begun to suggest that it may be possible to significantly reduce, if not eliminate the need for YAG capsulotomy.1 While surgical technique is unquestionably indispensable in this area, certain features of IOL design are identified as having displayed both historic and prospective benefits in reducing the likelihood of YAG capsulotomy. Specifically, the vertical edge configuration has demonstrated a substantial decrease in YAG capsulotomy rates to the 5% range, and this knowledge stems from the widespread acceptance of the MA60BM hydrophobic acrylic lens (Alcon Surgical, Fort Worth, TX) since 1995.
VERTICAL EDGE DESIGN
As a result of this intellectually stimulating vertical edge technology, considerable advances in the understanding of the pathogenesis of PCO have taken place. These advances have come in the form of large retrospective reviews, laboratory bench studies, and prospective evaluations of lens design in human subjects. Although this information is readily available from numerous sources, the goal of this article is to summarize the significant advances over the past 2 years in the struggle to eliminate PCO.
The major drawback of the vertical edge design has been the creation of dysphotopsias. Although some ophthalmologists dismiss dysphotopsias as another unavoidable result of cataract surgery, new advances in IOL design have shown great promise in curbing these disturbing side effects while preserving the benefit of the vertical edge. In the next issue of Cataract & Refractive Surgery Today, I will cover dysphotopsias and the designs to reduce them. Specifically, I will discuss the latest generation of edge-modified IOLs available in the US: the AcrySof models MA60AC and SA60AT (Alcon Surgical), the AMO Sensar with OptiEdge (Allergan Surgical, Irvine, CA), and the AMO ClariFlex (Allergan Surgical), a silicone IOL with the OptiEdge design.
POSTMORTEM PERSPECTIVEThe Ultimate Retrospective Review
At the Center for Research on Ocular Therapeutic and Biodevices at the Storm Eye Institute in Charleston, SC, David Apple, MD, et al published their ongoing research summarizing YAG capsulotomy rates on postmortem examination of 5,416 pseudophakic eyes.1 Although many specific areas related to PCO have been debated and investigated over the years (Table 1), the sheer volume of eyes examined in this study transcends these individual variations and establishes a solid foundation for examining the true long-term results of our efforts as cataract surgeons as they relate to PCO. Through this effort, the group identified six key factors, three surgeon-related and three IOL-related, that they believe have contributed to the rapidly decreasing capsulotomy rates of the past 2 decades.2 While these specific etiologies will continue to influence PCO in a given individual, attention to these factors should provide extensive benefits for preserving capsule clarity.
SURGEON-RELATED FACTORS
The surgeon-related factors include capsulorhexis to cover the entire optic edge,3 thorough cortical cleanup to the lens equator, and in-the-bag IOL fixation. The cadaver study has shown mixed results with regard to the surgeon-dependent factors over the study period. Modern small-incision cataract surgery with foldable IOLs has progressively improved the rate of in-the-bag IOL placement from 30% in the 1980s to 90% currently. However, cortical cleanup was cited as the key factor for the surgeon, and as the primary line of PCO defense of all six factors. While Dr. Apple identifies that surgical technique has significantly improved, Soemmering's ring formation in the autopsy study appears to be somewhat worse in the more recent specimens.4 Dr. Apple's group identified the appropriate use of Dr. I. Howard Fine's hydrodissection to cleave corticocapsular adhesions to facilitate cortical removal. More recently, my collaborative work with Dr. Apple5 has shown that irrigation with a J-cannula after nuclear removal will improve the speed, efficiency, and safety of cortical cleanup, and that this should also reduce the necessity for YAG capsulotomy.
IOL DESIGN FACTORS
The IOL design factors include “biocompatible” IOL material, maximal capsule contact by posterior-angled haptics and posterior optic convexity, as well as a squared-off barrier edge to create a capsular bend. The study cited the key feature for IOLs, and the second line of defense overall, as the posterior barrier edge. This squared-off edge induces the capsule to bend at the optic edge as the capsule heals following cataract extraction, and this bend is directly the result of the convergence of the surgeon and IOL factors for a clearer posterior capsule.
Inducing a Capsular Bend
In examining how the barrier edge reduces PCO, it is important to understand how the capsule heals around this edge to create a capsular bend. I found the recent conclusion of a prospective study performed by Rupert Menapace, MD, et al and presented at the 2001 ESCRS meeting in Amsterdam to be rather surprising. Dr. Menapace developed a technique of bimanual irrigation and aspiration that allowed for complete polishing of the underside of the anterior capsule. The polishing kept the anterior capsule clearer; however, it was found that this technique actually increased the likelihood of YAG capsulotomy. The key advancement from this study is that the fibrosis of the anterior capsule, initiated by the anterior epithelial cells, is necessary to form the capsular bend to inhibit cellular migration.
Formation of the bend begins as the anterior capsule adheres to the anterior surface of the optic (Figure 1A). Increased adherence and/or initiation of capsular fibrosis are considered to be properties of both hydrophobic acrylic and later-generation silicone IOLs. Next, the peripheral capsular leaflets begin to adhere from the periphery toward the edge of the optic (Figure 1B and C). At the optic border, the posterior capsule is drawn toward the fibrosing anterior capsule, now tightening against its adherence to the anterior optic surface (Figure 1D). Where the capsulorhexis has slipped off the edge of the optic, the physical bend cannot effectively form. The bend created at the posterior optic edge provides a perpendicular discontinuity that has been shown to effectively block lens epithelial cell migration in cell culture, animal, and prospective human studies.6-8
THE NEXT CRITICAL QUESTION
From the perspective of examining IOLs for benefits in reducing PCO, which is more important: the material or the design? In 1997, Linnola9 identified the increased presence of fibronectin and vitronectin as an extracellular matrix accounting for increased capsular adherence of acrylate lenses over PMMA, silicone, or hydrogel IOLs. This “sandwich” theory was proposed as an explanation of the decreased rate of PCO with the AcrySof lenses, and helps explain how the posterior capsule can actually become clearer with time. Unfortunately, the cadaver-eye study did not include square-edge IOLs of the other materials.
Nishi et al6 studied rabbit eyes implanted with the AcrySof MA60BM with the intact sharp vertical edges, and two altered versions with separately rounded or tumble-polished edges. Whereas the capsular adhesion was maintained due to the unaltered material surface, the rounded edge lost all protective benefits in reducing PCO, and behaved similarly to other round-edge IOLs previously studied. In this article, Dr. Nishi speculates that the speed of bend formation is paramount in preventing cellular migration into the space behind the optic. This put to rest the question of material adhesion versus design by the demonstrated effect of the vertical barrier edge in creating the capsular bend. In his most recent study, Dr. Nishi commented that a discontinuous capsular bend created by an IOL with sharp optic edges might inhibit the migration of lens epithelial cells regardless of the type of lens material.8
A more recent study by Shauersberger10 showed equal rates of PCO between two square-edge IOLs of differing hydrophobic materials at 3-year follow-up. The 6-mm AcrySof lens with 13-mm PMMA haptics and the 6-mm CeeOn silicone lens (Pharmacia, Kalamazoo, MI) with 12-mm polyvinylidene fluoride haptics were implanted to evaluate the human uveal and capsular biocompatibility between these two materials. The lack of clinical difference in PCO rates between these two lenses was not surprising. The silicone lens performed better in regard to intralenticular glistenings as well as the absence of giant cell deposits, and the acrylic lens demonstrated less anterior capsular opacification, but greater retention of surface lens epithelial cell growth. However, none of these differences was clinically significant.
James McCulley, MD, has discussed the issues of capsular biocompatibility as being ?biostimulatory,? ?biostatic,? or ?biotoxic.? These terms summarize the reaction of the anterior lens epithelial cells when in contact with the IOL material. As a simple observation, it seems inappropriate to term second-generation silicone as an IOL ?biotoxic,? in light of the superior uveal biocompatibility of the human eye and this material. At present, studies comparing hydrophilic acrylic lenses with biostimulatory characteristics, to either hydrophobic acrylic or second-generation silicone with biostatic and biotoxic capsular responses, respectively, show a general trend toward PCO with hydrophilic acrylic lenses.
HAPTIC DESIGN AND CAPSULAR BEND FORMATIONNot All Vertical Edges Are Barrier Edges
It then becomes an issue of a “biocompatible” IOL material appropriate to incite just the right amount of anterior capsule fibrosis, but without stimulating the growth of lens epithelial cells. This material, with the proper optic barrier edge design, should reduce PCO. The third feature of the IOL, haptic angulation and optic design, now comes into play in determining whether a capsular bend will be consistently created.
In Dr. Apple's study, the IOLs found to have the lowest incidence of PCO were those that had the greatest “maximal capsule contact.” This has also been discussed for some time as “no space, no cells.” We see from the example of the MA60BM with its 10º posterior haptic angulation that the posterior convexity of the optic is pressed into the posterior capsule (Figure 2). This feature provides the counterforce to the fibrosis of the anterior capsule and allows the contracting posterior capsule to bend as it pulls tightly over the vertical edge of the optic, while blocking the migration of equatorial epithelial cells into the space behind the optic.
Meacock et al found a significant benefit in the larger optic of the MA60BM versus the 5.5-mm optic of the MA30BM.11 The larger 6-mm surface area provides a 16% greater apposition to the capsule. The same group also reported on the interaction of the haptic compression force and the optic.12 Comparing two identical designs but two different materials, the Storz P49UV PMMA IOL (Bausch & Lomb, Claremont, CA) was tested against the Hydroview H60M (Bausch & Lomb). Considerable linear capsular folds were seen to persist at 6 months in the Hydroview group, attributable to a lower rate of haptic compression force decay. These investigators speculated that the presence of linear folds in the posterior capsule longer than 1 month may be a factor leading toward increased rates of PCO. Unfortunately, the propensity of LEC proliferation with the hydrophilic acrylic material overshadowed the study design.
At the 2001 ESCRS meeting in Amsterdam, Nishi et al presented the effect of a larger optic and bulky haptic design on the formation of a capsular bend. The SA30AL (Alcon Surgical) was evaluated in its unaltered form, and in an experimental model with a 7-mm optic. In this rabbit eye study, the bulky haptics were found to prevent the anterior and posterior capsule leaflets from fusing at the vertical edge of the optic, specifically at the junction of the optic and haptic. In this instance, a vertical edge is not a true barrier edge as the capsular bend was actually defeated by the haptic design (Figures 3 and 4).
RETAINED CORTEX AND THE BARRIER EDGEA Rabbit Eye Perspective
Rabbits have been the laboratory animal of choice for evaluating IOL design and PCO development for some time. The rabbit is relatively easy to maintain, and its lens is only slightly larger than the human lens. The speed of capsule reaction in the rabbit is also favorable for evaluating the effects of design. Typically, 3 to 4 weeks postcataract surgery in the rabbit correlates to 2 to 3 years of human healing. Dr. Nishi has specifically cited that after the 3-week point, the aggressive regeneration of lens epithelial cells may overwhelm the subtleties of the features of healing.
Obviously, it is impossible to fully evaluate an IOL design in perspective to human capsular bag healing prior to having the IOL in widespread use. Although our current experience with the MA60BM now extends in the US to over 6 years, there are no features of the design that provide controversy with regard to long-term ocular stability and success. Postmortem examination of this lens has demonstrated its success in reducing PCO and correlates well with rabbit eye studies.
The evaluation period of the SA60AT is much shorter in human eye studies. Experience with this lens in the US now approaches a mere 2 years and only in select sites. Rabbit eye studies of this IOL, as performed in Dr. Apple's laboratory, have demonstrated a benefit in maintaining low rates of PCO relative to other one-piece acrylic IOLs available in Europe. While haptic stability was not one of the features specifically evaluated in the study presented by Luis Vargas, MD, at the 2001 ESCRS meeting, two different Miyake-Apple views of the SA60AT show the haptic slightly bent back to overlap the optic. The distortion of the bulky haptic with very little outward compressive force was caused by regenerative cortex from the periphery pressing it inward (Figure 5A and B).
In these instances, not only do the planar haptics of the SA60AT fail to press the optic into the posterior capsule to facilitate the capsular bend, the haptic may be directly responsible for defeating it physically as the cortex regenerates. It is quite possible that the lower rate of human lens epithelial cell proliferation, combined with improved cortical removal techniques, may avoid the consequence of the haptic bent back onto the optic in human use. However, the simple flaws in creating a capsular bend from a vertical edge with this haptic design are evident prior to this potential difficulty becoming apparent in the clinical setting.
THE FUTURE PERSPECTIVEThe Capsular Bending Ring
It seems that the most exciting and innovative work is currently beyond the reach of most surgeons in the US. Nishi and Menapace have used a modified capsular tension ring to stem PCO in the far periphery of the capsule.13 This ring, termed the capsular bending ring, is 11 mm in diameter and 0.7 mm in anterior-posterior depth. The ring has sharp edges, and was placed in the capsule before the implantation of a Hydroview hydrophilic acrylic lens with its higher rate of LEC proliferation and PCO. The ability of this ring to block PCO relative to its absence was definitive, but not complete. The evaluated model had a small breach in the barrier where the ends met, which these investigators speculated allowed migration of the equatorial epithelial cells toward the optic.
Although the anterior capsule was not polished, the capsule did not achieve contact with the IOL in the presence of the ring, and the anterior capsule maintained transparency without fibrosis or shrinkage. This was in comparison to 100% of the control Hydroview group demonstrating fibrosis. With the ring, no LEC migration could be identified, but 25% of the control Hydroview lenses had LEC migration. The investigators summarized that the best place to create the discontinuous bend would be the equatorial periphery for patients at greatest need for transparent anterior and posterior capsules, such as children and those at risk for future vitreoretinal surgery.
SUMMARY
The vertical edge technology has provided our field with an exciting tool to reduce the morbidity and expense of PCO. From evaluations of this design, we now can make considerable sense of seemingly counterintuitive findings from previous studies performed without this edge. Strict adherence to good modern small-incision surgical technique will be increasingly more important to allow our patients the benefits of this technology. Only one barrier remains to keep patient satisfaction high: reducing the dysphotopsias that this edge can create. In the continuation of this article, I will discuss new IOL designs featuring edges designed to specifically improve patient satisfaction.
1. Apple D, Peng Q, Visessook N, et al: Eradication of posterior capsule opacification: Documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained postmortem. Ophthalmology 108:505-518, 2001
2. Apple D, Werner L, Pandey S: Newly recognized complications of posterior chamber intraocular lenses. Arch Ophthalmol 119:581-582, 2001
3. Ravalico G, Tognetto D, Palomba M, et al: Capsulorhexis size and posterior capsule opacification. J Cataract Refract Surg 22:98-103, 1996
4. Apple D, Peng Q, Visessook N, et al: Surgical prevention of posterior chamber opacification. J Cataract Refract Surg 26:180-187, 2000
5. Dewey SH: Subincisional Cortical Removal Simplified by J-Cannula Irrigation. J Cataract Refract Surg 28:11-14, 2002
6. Nishi O, Nishi K, Sakanishi K: Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens. Ophthalmic Surg Lasers 29:587-594, 1998
7. Nishi O, Nishi K, Wickstrom K: Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 26:1543-1549, 2000
8. Nishi O, Nishi K, Akura J, Nagata T: Effect of round-edged acrylic intraocular lenses on preventing posterior capsule opacification. J Cataract Refract Surg 27:608-613, 2001
9. Linnola R: Sandwich theory: Bioactivity-based explanation for posterior capsule opacification. J Cataract Refract Surg 23:1539-1542, 1997
10. Schauersberger J, Amon M, Kruger A: Comparison of the biocompatibility of 2 foldable intraocular lenses with sharp optic edges. J Cataract Refract Surg 27:1579-1585, 2001
11. Meacock W, Spalton D, Boyce J, Jose R: Effect of optic size on posterior capsule opacification: 5.5 mm versus 6.0 mm AcrySof intraocular lenses. J Cataract Refract Surg 27:1194-1198, 2001
12. Meacock W, Spalton D: Effect of intraocular lens haptic compressibility on the posterior lens capsule after cataract surgery. J Cataract Refract Surg 27:1366-1371, 2001
13. Nishi O, Nishi K, Menapace R, Akura J: Capsular bending ring to prevent posterior capsule opacification: 2 year follow-up. J Cataract Refract Surg 27:1359-1365, 2001
14. Tetz M, Nimsgern C: Posterior capsule opacification. Part 2: Clinical findings. J Cataract Refract Surg 25:1662-1674, 1999
