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   Table of Contents      
Year : 2004  |  Volume : 52  |  Issue : 2  |  Page : 99-112

Posterior Capsule Opacification : A Review of the Aetiopathogenesis, Experimental and Clinical Studies and Factors for Prevention

Department of Ophthalmology and Visual Sciences, University of Utah, 50 North Medical Drive, Salt Lake City, Utah, USA

Correspondence Address:
Suresh K Pandey
Department of Ophthalmology and Visual Sciences, University of Utah, 50 North Medical Drive, Salt Lake City, Utah
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Source of Support: None, Conflict of Interest: None

PMID: 15283214

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Posterior capsule opacification (PCO, secondary cataract, after cataract) is a nagging postsurgical complication following extracapsular cataract surgery (ECCE) and intraocular lens (IOL) implantation. PCO should be eliminated since it has deleterious sequelae and Neodynium: Yttrium Aluminium Garnet (Nd: YAG) laser treatment often is an unnecessary financial burden on the health care system. PCO following cataract surgery could be a major problem, since patient follow-up is difficult and the Nd:YAG laser is not always available. Advances in surgical techniques, IOL designs/biomaterials have been instrumental in bringing about a gradual and unnoticed decrease in the incidence of PCO. We strongly believe that the overall incidence of PCO and hence the incidence of Nd:YAG laser posterior capsulotomy is now rapidly decreasing - from 50% in the 1980s and early 1990s to less than 10% currently. Superior tools, surgical procedures, skills and appropriate IOL designs have all helped to significantly reduce this complication. In this article, we review the aetio pathogenesis, experimental and clinical studies and propose surgical and implant-related factors for PCO prevention. Careful application and utilisation of these factors by surgeons could lead to a significant reduction is secondary cataract, the second most common cause of visual loss worldwide

Keywords: Intraocular lens, posterior capsule opacification, posterior capsulotomy, secondary cataract, sealed capsule irrigation

How to cite this article:
Pandey SK, Apple DJ, Werner L, Maloof AJ, Milverton E J. Posterior Capsule Opacification : A Review of the Aetiopathogenesis, Experimental and Clinical Studies and Factors for Prevention. Indian J Ophthalmol 2004;52:99-112

How to cite this URL:
Pandey SK, Apple DJ, Werner L, Maloof AJ, Milverton E J. Posterior Capsule Opacification : A Review of the Aetiopathogenesis, Experimental and Clinical Studies and Factors for Prevention. Indian J Ophthalmol [serial online] 2004 [cited 2022 Sep 27];52:99-112. Available from: https://www.ijo.in/text.asp?2004/52/2/99/14613

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Opacification of the posterior capsule caused by postoperative proliferation of cells in the capsular bag remains the most frequent complication of cataract-intraocular lens (IOL) surgery.[1],[2] In addition to classic posterior capsule opacification (PCO, secondary cataract, after cataract), postoperative lens epithelial cell (LEC) proliferation is also involved in the pathogenesis of anterior capsule opacification/fibrosis (ACO) and inter-lenticular opacification (ILO). [3],[4],[5],[6] Secondary cataract (PCO) has been recognised since the origin of extracapsular cataract surgery (ECCE) and was noted by Sir Harold Ridley in his first IOL implantations.[7],[8] It was particularly common and severe in the early days of IOL surgery (in the late 1970s and early 1980s) when the importance of cortical cleanup was less appreciated. Through the 1980s and early 1990s, the incidence of PCO ranged between 25-50%.[9] PCO is a major problem in paediatric cataract surgery where the incidence approaches 100%. [10],[11],[12]

One of the crowning achievements of modern cataract surgery has been a gradual, almost unnoticed decrease in the incidence of this complication. Our data at present show that with modern techniques and IOLs, the expected rate of PCO and the subsequent Neodynium: Yttrium Aluminium Garnet (Nd: YAG) laser posterior capsulotomy rate is decreasing to a single digit (less than 10%).[13],[14]

In this article we review the aetiopathogenesis and published studies on PCO, and present information that supports the very optimistic prediction of rapidly decreasing incidence of secondary cataract, the second commonest cause of visual loss worldwide. Most of the information provided in this review is based on several experimental studies on the pathogenesis and treatment of PCO in our laboratory during the past 20 years, and after compiling information from other experimental and clinical studies from several centers worldwide. It is hoped that this discussion provides relevant information and guidance regarding PCO and its prevention and that it will increase surgeons' awareness of the various tools now available to eradicate this complication.

  Why Eradicate Posterior Capsule Opacification? Top

Although cataract is the most common cause of blindness in the world, after-cataract (PCO or secondary cataract) is an extremely common cause as well. The eradication of PCO following ECCE has major medical and financial implications:

1. Nd: YAG laser secondary posterior capsulotomy, can be associated with significant complications. Potential problems include IOL optic damage/pitting, postoperative intraocular pressure (IOP) elevation, cystoid macular oedema, retinal detachment, and IOL subluxation. [15],[16],[17],[18]

2. Dense PCO and secondary membrane formation is particularly common following paediatric IOL implantation. [10],[11],[12] A delay in diagnosis can cause irreparable amblyopia.

3. PCO represents a significant cost to the health care system. In the USA. Nd:YAG laser treatments of almost one million patients per year cost up to $250 million annually.[9]

4. A posterior capsulotomy can increase the risk of posterior segment complications in high myopes and patients with uveitis, glaucoma, and diabetic retinopathy.

5. PCO of even a mild degree can decrease near acuity through a multifocal IOL, and may interfere with the function of refractive/accommodating IOL designs.

6. A significant incidence of PCO means that cataract surgery alone may not restore lasting sight to the 25 million people worldwide who are blind from cataract.[19]

7. Finally, a successful expansion of ECCE-IOL surgery in the developing world depends on eradication, or at least reduction of PCO, since patient follow-up is difficult and access to the Nd:YAG laser is not widely available.[19]

  Aetiopathogenesis Top

In the normal crystalline lens, the LECs are confined to the anterior surface at the equatorial region and the equatorial lens bow. This single row of cuboidal cells can be divided into two different biological zones [Figure - 1].

A. The anterior-central zone (corresponding to the zone of the anterior lens capsule) consists of a monolayer of flat cuboidal, epithelial cells with minimal mitotic activity. In response to a variety of stimuli, the anterior epithelial cells ("A" cells) proliferate and undergo fibrous metaplasia. This has been termed "pseudofibrous metaplasia" by Font and Brownstein.[20]

B. The second zone is important in the pathogenesis of "pearl" formation. This layer is a continuation of anterior lens cells around the equator, forming the equatorial lens bow ("E" cells). Unlike within the A-cell layer, cell mitoses, division, and multiplication are quite active in this region. New lens fibres are continuously produced in this zone throughout life.

In addition to classic PCO, postoperative LEC proliferation is also involved in the pathogenesis of other entities, such as anterior capsule opacification/fibrosis (ACO)[3],[4] and ILO; a more recently described complication related to piggyback IOLs.[5],[6] Thus, there are three distinct anatomic locations within the capsular bag where clinically significant opacification may occur postoperatively [Figure - 1]. Ophthalmic researchers are now developing surgical techniques/devices not only to eliminate PCO, but also to eliminate capsular bag opacification, secondary to proliferation of LECs.

Although both types of cells (from the anterior central zone and from the equatorial lens bow) have the potential to produce visually significant opacification, most cases of classic PCO are caused by proliferation of the equatorial cells. The term posterior capsule opacification is actually a misnomer. It is not the capsule which opacifies; rather, an opaque membrane develops as retained cells proliferate and migrate onto the posterior capsular surface.

The opacification usually takes one of two morphologic forms. One form consists of capsular pearls , which can consist of clusters of swollen, opacified epithelial "pearls" or clusters of posteriorly migrated equatorial epithelial (E) cells (Bladder or Wedl cells) [Figure - 2]. It is probable that both LEC types can also contribute to the fibrous form of opacification. Anterior epithelial (A) cells are probably important in the pathogenesis of fibrous PCO, since the primary type of response of these cells is to undergo fibrous metaplasia. Although the preferred type of growth of the equatorial epithelial (E) cells is in the direction of bloated, swollen, bullous-like bladder (Wedl) cells, these also may contribute to formation of the fibrous form of PCO by undergoing a fibrous metaplasia. This is a particularly common occurrence in cataracts in developing world settings where cataract surgery has been delayed for many years, and where posterior subcapsular cataracts have turned into fibrous plaques [Figure - 3].[21]

Capsulorhexis contraction (capsular phimosis) is an important complication related to extreme fibrous proliferation of the anterior capsule. [2],[3],[4] Capsular phimosis can be avoided by not making the capsulorhexis too small. In general, a diameter less than 5.5 mm is undesirable.

In contrast to the lesions of the anterior (A cells) capsule that cause phenomena related to fibrosis, the E cells of the equatorial lens bow [Figure - 1] tend to form cells that differentiate toward pearls (Bladder cells) and cortex. Equatorial cells (E-cells) are also responsible for formation of a Soemmering's ring. The Soemmering's ring, a dumb-bell or donut shaped lesion that often forms following any type of rupture of the anterior capsule, was first described in connection with ocular trauma. The pathogenetic basis of a Soemmering's ring is rupture of the anterior lens capsule with extrusion of nuclear and some central lens material. The extruded cortical remnants then transform into Elschnig pearls [Figure - 2]. It is not widely appreciated that a Soemmering's ring forms virtually every time any form of ECCE is done, whether manual, automated or with phacoemulsification. This material is derived from proliferation of the epithelial cells (E-cells) of the equatorial lens bow. We have noted that these cells have the capability to proliferate and migrate posteriorly across the visual axis, thereby opacifying the posterior capsule. Because the Soemmering's ring is a direct precursor to PCO, surgeons should strive to prevent its formation.

Cell types other than lens epithelial may be involved in PCO. As ECCE is always associated with some breakdown of the blood-aqueous barrier, inflammatory cells, erythrocytes, and many other inflammatory mediators may be released into the aqueous humor. The severity of this inflammatory response may be exacerbated by the IOL. This foreign body elicits a three-stage immune response that involves many different cell types, including polymorphonuclear leukocytes, giant cells, and fibroblasts. Collagen deposition onto the IOL and the capsule may cause opacities and fine wrinkles to form in the posterior capsule. In most cases, however, this inflammatory response is clinically insignificant. Iris melanocytes also have been shown to adhere to and migrate over the anterior surface of the posterior capsule.

  Clinical Manifestations and Treatment Top

The interval between surgery and PCO varies widely, ranging from three months to four years after the surgery. Although the causes of PCO are multifactorial as reported in several studies,[9],[22],[23] there is an inverse correlation with age. Young age is a significant risk factor for PCO, and its occurrence is a virtual certainty in paediatric patients. [10],[11],[12]

Visual symptoms do not always correlate to the observed amount of PCO. Some patients with significant PCO on slitlamp examination are relatively asymptomatic while others have significant symptoms with mild apparent haze, which is reversed by capsulotomy.[24]

Visually significant PCO is usually managed by creating an opening within the opaque capsule using the Nd: YAG laser. A surgical posterior capsulotomy may be indicated in children for dense PCO associated with secondary membrane formation. The technical details, parameters, preoperative and postoperative treatment, complications and recommendations for surgical and Nd: YAG laser posterior capsulotomy are discussed in the literature. [15],[16],[17],[18] In brief, indications for Nd: YAG laser capsulotomy include presence of a thickened capsule leading to functional impairment of vision and the need to evalu-ate and treat posterior segment pathology. However, caution should be exercised if there is any signs suggestive of intraocular inflammation, raised IOP, macular oedema, and a predisposition to retinal detachment (e.g. high myopia). As mentioned before Nd: YAG laser posterior capsulotomy may be rarely associated with complications such as transient rise in IOP, enhanced risk of retinal detachment, particularly marked in axial myopia, cystoid macular oedema, IOL subluxation, lens optic damage/pitting, endophthalmitis, vitreous prolapse into the anterior chamber and anterior hyaloid disruption.

Six Factors for Prevention of Posterior Capsule Opacification

PCO prevention has been our active research interest since 1982. Based upon 20 years of research experience on evaluation of around 17,500 IOL related specimens (7523 human eyes obtained postmortem; 6127 eyes implanted with rigid lenses and 1396 eyes implanted with foldable lenses) using the Miyake-Apple technique, and published studies from our center,[1],[9],[13],[14],[19], [25],[26],[27],[28],[29],[30] we have reviewed the principles of PCO prevention. These measures can be divided into two categories. One strategy is to minimise the number of retained/regenerated LECs and cortex through thorough cortical cleanup. The second strategy is to prevent the remaining LECs from migrating posteriorly. The edge of the IOL optic is critical in the formation of such a physical barrier.

We have identified three surgery-related factors and three IOL-related factors that are particularly important in the prevention of PCO [Table - 1]. [25],[26],[27],[28],[29],[30]

  Surgery-related factors to reduce PCO Top

Hydrodissection-enhanced cortical cleanup: A very important and underrated surgical step is hydrodissection. Fine perfected and popularised this technique and coined the term cortical cleaving hydrodissection.[31] Until fairly recently, many surgeons had a rather fatalistic attitude towards removal of lens cortex and cells during (manual / automated - or with phacoemulsification). A common opinion was that it removal of all or even most equatorial cells from the bag is impossible. PCO was therefore considered an inevitable complication.[9]

The necessary tenting up of the anterior capsule during subcapsular (or cortical cleaving) hydrodissection is best achieved by using a cannula bent at the tip allowing a flow of fluid toward the capsule to efficiently separate capsule from cortex [Figure - 4]. By freeing and rotating the lens nucleus, hydrodissection facilitates lens nucleus and cortex removal without zonular-capsular rupture.[32] We now know from autopsy and experimental studies that thorough cortical and cellular cleanup from the capsular bag can be accomplished in most cases.[27] In our study we demonstrated that use of hydrodissection during cataract surgery allowed more efficient removal of cortex and LECs, (which in turn reduces PCO), compared to control eyes where hydrodissection was not utilised [Figure - 4].[27] Occasionally this can even occur without the need for cortical aspiration with a separate irrigation/aspiration instrument.

Surgeons use balanced salt solution while performing cortical cleaving hydrodissection. Recent experimental animal studies from our center have shown that use of preservative-free lidocaine 1% during hydrodissection may diminish the amount of live LECs by facilitating cortical cleanup, loosening the desmosomal area of cell-cell adhesion with decreased cellular adherence, or by a direct toxic effect.[33] Corneal endothelial toxicity continues to be a major concern of using hypo-osmolar agents (to loosen the cell-cell adhesion) during hydrodissection or any step of cataract surgery, in absence of a sealed capsular bag. However, it is now possible to irrigate the entire capsular bag using an injection-molded silicone disposable innovative device known as Perfect Capsule (Milvella, Sydney, Australia). Sealed capsule irrigation (SCI) isolates the internal lens capsule, and facilitates removal of residual cortical material as well as lens epithelial cells, and thus prevents/delays capsular bag opacification.[34],[35] The SCI technique is pioneered by one of us (AJM), and discussed in detail later in this article.

In-the-bag (capsular) fixation : The hallmark of modern cataract surgery is the consistent and secure in-the-bag (capsular) fixation [Table - 1]. The most obvious advantage of in-the-bag fixation are the accomplishment of good optic centration and sequestration of the IOL from adjacent uveal tissues. Numerous other advantages have been described elsewhere.[36],[37] This also reduces the amount of PCO.

One desired goal of in-the-bag fixation is enhancing the IOL optic barrier effect. This is maximised when the lens optic stays fully in-the-bag and is in direct contact with the posterior capsule. In case one or both haptics are not placed in the bag, a potential space is created, allowing an avenue for cells to grow posteriorly toward the visual axis. The reader may recall the barrier ridge IOL design of Kenneth Hoffer in the 1980s. This was not favoured at that time.[9] The reason was not a problem with the concept or the IOLs themselves, but rather that only about 30% of posterior chamber IOLs were implanted inside the bag during this time.

The in-the-bag fixation of IOLs occurs about 60% of the time in non-phaco ECCE. In many cases this is due to combination of rigid design IOLs and can-opener anterior capsulotomies. With the modern foldable lens implantation, in-the-bag fixation has increased to over 90%. It is not the foldable IOL , or the small incision that has contributed to this success, rather it is the meticulous surgery including a continuous curvilinear capsulorhexis (CCC) and secures implantation of both IOL loops in the bag.[25]

Capsulorhexis edge on IOL surface . A less obvious, but significant addition to precise in-the-bag fixation, is creating a CCC diameter slightly smaller than that of the IOL optic. For example, if the IOL optic were 6.0 mm, the capsulorhexis diameter would ideally be slightly smaller, perhaps 5.0-5.5 mm. This places the cut anterior capsule edge on the anterior surface of the optic, providing a tight fit (analogous to a "shrink wrap") and helping to sequester the optic in the capsular bag from the surrounding aqueous humor [Table - 1]. This mechanism may support protecting the milieu within the capsule from at least some potentially deleterious factors within the aqueous, especially some macromolecules, and some inflammatory mediators. The concept of capsular sequestration based on the CCC size and shape is subtle, but more and more surgeons appear to be applying this principle and seeing its advantages.

  Three IOL-Related Factors to Reduce PCO Top

A. IOL biocompatibility . Lens material biocompatibility [Table - 1] is an often-misunderstood term. It can be defined by many criteria, e.g. the ability to inhibit stimulation of epithelial cellular proliferation.[38] The less the cell proliferation the lower the chance for secondary cataract formation. In our large series of postmortem human eyes, the Alcon AcrySof" IOLs presented with minimal to absent Soemmering's ring formation, PCO and ACO [Figure - 5]. [1],[2],[3],[4],[13],[14],[26],[36] In addition, the amount of cell proliferation is greatly influenced by surgical factors, such as copious cortical cleanup. Furthermore, the time factor also plays a role, such as the duration of the implant in the eye. Additional longterm studies are required to assess the overall role of "biocompatibility" in the pathogenesis of PCO.

B. Maximal IOL Optic-Posterior Capsule Contact. Other contributing factors in reducing PCO are posterior angulation of the IOL haptic and posterior convexity of the optic [Table - 1]. This is due to the creation of a "shrink wrap", a tight fit of the posterior capsule against the back of the IOL optic. The relative "stickiness" of the IOL optic biomaterial probably helps produce an adhesion between the capsule and IOL optic. There is preliminary evidence that the hydrophobic acrylic IOL biomaterial provides enhanced capsular adhesion, or "bioadhesion". [39],[40],[41] This will require further study.

C. Barrier Effect of the IOL Optic. The IOL optic barrier effect [Table - 1] plays an important role as a second line of defense against PCO, especially in cases where retained cortex and cells remain following ECCE. The concept of the barrier effect goes back to the original Ridley lens.[8] If accurately implanted in the capsular bag, it provides an excellent barrier effect, with almost complete filling of the capsular bag and contact of the posterior IOL optic to the posterior capsule ("no space, no cells"). A lens with one or both haptics "out-of-the-bag" has much less of a chance to produce a barrier effect. Indeed, the IOL optic's barrier function has been one of the main reasons that PC-IOLs implanted after ECCE throughout the decades did not produce an unacceptably high incidence of florid PCO.

A subtle difference between classic optics with a round tapered edge and optics with a square truncated edge became evident recently [Table - 1]. The effect of a square-edge optic design as a barrier was first discussed by Nishi et al [42],[43],[44] in articles related to PCO. In a clinicopathological study, our laboratory confirmed this phenomenon in human eyes [Figure - 6].[27],[28] We reported our results of a large histopathological analysis covering the IOL barrier effect, with special reference to the efficacy of the truncated edge [Figure - 6]. A truncated, square-edged optic rim appears to cause a complete blockade of cells at the optic edge, preventing epithelial ingrowth over the posterior capsule. [45],[46],[47],[48],[49],[50],[51],[52] The enhanced barrier effect of this particular edge geometry provides another supplemental factor, in addition to the five above-mentioned factors, that has significantly diminished the overall incidence of clinical PCO.

Our past studies [13],[14], demonstrated that the original three-piece MA60 AcrySof" (Alcon Inc., Fort Worth, TX) IOL successfully combined these three IOL-related factors [Table - 1], [Figure - 5], [Figure - 6] in a way that produced a major PCO advantage. Other manufacturers have begun to incorporate these PCO preventing features, such as a sharp, or squared-posterior edge. The Cee-On 911™ silicone IOL (Pfizer Inc., New York, NY) was the first silicone IOL to feature a squared edge. The Sensar™ hydrophobic acrylic (Advanced Medical Optics Inc., Santa Ana, CA) and Clariflex™ silicone (Advanced Medical Optics Inc, Santa Ana, CA) IOLs now feature a sharp posterior edge, combined with a rounded anterior edge. Modification in the Centerflex‚ one-piece hydrpophilic IOL design (Rayner Inc., Hove East Sussex, UK) has been incorporated to prevent cellular ingrowth at the broad optic-haptic junction. The modified profile provides a square edge (barrier, ridge, wall) for 360 degrees around the lens optic (enhanced square edge), eliminating the potential defect [Figure - 7]. This further minimizes the ingrowth of migrating LECs toward the visual axis.

A major disadvantage of the truncated edge is the production of clinical visual aberrations, such as glare, halos and crescents.[53] Subtle manufacturing changes in manufacturing help alleviate glare and other optical complications. [Figure - 8] illustrates scanning electron microscopy of the single-piece AcrySof® (SA30AL) IOL showing the square (truncated) edge of the optic that had a matte (velvet or ground-glass) appearance, a feature that may minimise edge glare and other visual phenomena. Another example of design modification include introduction of sensar optic Edge‰ IOL manufactured by Advanced Medical Optics. This IOL has a squared posterior edge and a round anterior edge [Figure - 9]. Therefore, it avoids optical dysphotopsias, while retaining the PCO beneficial squared posterior edge.

  Confirmation of Six factors in the Laboratory and Clinical Studies Top

A review of literature.[9],[22],[23],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52] along with experimental studies from our center[14], [27],[28],[29],[30] and a complete analysis of our large series of eyes obtained postmortem [1],[2],[3],[4],[13],[36] have helped us develop the above mentioned six factors that we believe greatly contribute to the reduction of PCO. Furthermore, an analysis of Nd: YAG laser posterior capsulotomy rates among nine commonly used IOL models has led us to the optimistic conclusion that the incidence of PCO is rapidly diminishing, at least in the industrialised world. [Table 2 ]shows the ranking of the Nd: YAG laser posterior capsulotomy rates (%) evaluated in a total of 7523 pseudophakic human eye obtained postmortem (between January 1988 and July 2002) at our center. Note the lowest percentage of Nd: YAG laser posterior capsulotomy (at the top) and the relatively older, (rigid lenses and early foldable lens designs) had shown higher Nd: YAG laser posterior capsulotomy rate (shown at the bottom of the table [unpublished data]. The three lenses with the lowest posterior capsulotomy rates ranging between 0% and 12.20% are modern designs, mostly implanted after 1992 in contrast to the remaining six lenses with the higher rates ranging between 20.2% and 31.5%. These were all older designs, already in the database prior to 1992. In order to evaluate the influence of lens quality versus the influence of the surgical technique on the PCO/Nd: YAG laser posterior capsulotomy rates, it is useful to follow a trend-line in the longterm. Under optimal conditions, but not possible in this analysis, the information should be viewed considering the age and the duration of each implant. One of the important limitations in most of the studies of pseudophakic human eyes obtained postmortem from our center [1],[2],[3],[4],[13],[36], was lack of detailed information such as dates of IOL implantation or the time between implantation and death. These details were difficult to determine due to ethical considerations. These variables are going to factor out over time as larger numbers are obtained and the trend "time line" is extended.[13]

  Confirmation of the six factors in clinical studies Top

We would like to cite three studies that confirm the advantage of applying one or more surgical/IOL related factors to prevent or delay PCO formation. Firstly, a clinical study, by Ram and associates[54] confirmed previous pathological studies demonstrating the importance of in-the-bag fixation of posterior chamber (PC) IOLs (both rigid and foldable) in reducing the incidence of PCO. This is true for both standard ECCE and phacoemulsification. This study comprised 278 eyes of 263 patients following ECCE and 318 eyes of 297 patients following phacoemulsification with PC IOL implantation. The presence of a visually significant PCO (a decrease in Snellen visual acuity of 2 or more lines) and IOL haptic fixation were evaluated postoperatively using slitlamp biomicroscopy. Haptic position was noted as in-the-bag (B-B), 1 haptic in the bag and 1 in the sulcus (bag-sulcus [B-S]), or both haptics out of the bag (sulcus-sulcus [S-S]). In addition, the rate of visually significant PCO was compared among 3 IOL biomaterials: poly methyl methacrylate, silicone, and hydrophobic acrylic. Visually significant PCO occurred in 42.45% of eyes receiving ECCE and 19.18% of eyes receiving phacoemulsification (P <.001, chi-square test) after a mean follow-up of 2.4 ± 0.7 years. In both groups, visually significant PCO was significantly less in eyes with B-B fixation than in those with B-S or S-S fixation (P <.001). The rate of visually significant PCO in all eyes in the phacoemulsification group with B-B fixation was low (11.90%) and was significantly lower in eyes with a hydrophobic acrylic IOL (2.22%; P <.05, chi-square test). The results of this study suggested in-the-bag PC IOL fixation reduces the incidence of PCO. Thorough removal of lens substance, including hydrodissection-assisted cortical cleanup, and in-the-bag PC IOL fixation seem to be the most important surgical factors in reducing PCO, regardless of surgical procedure or IOL type used.

Ravalico and associates[55] determined the ideal capsulorhexis size for minimising the incidence of PCO. These authors retrospectively evaluated 107 patients who had extracapsular cataract extraction with capsulorhexis and capsular bag IOL implantation. The PCO site (central, paracentral, and peripheral) and degree (mild, moderate, and severe) were evaluated in relation to the capsulorhexis edge location relative to the IOL optic. Patients were divided into three groups. Group 1: capsulorhexis free edge located on the IOL optic for 360 degrees; Group 2: capsulorhexis free edge located asymmetrically on and peripherally to the IOL optic; Group 3: capsulorhexis free edge located peripherally to IOL optic for 360 degrees. The results of this study demonstrated that in Groups 1 and 2, the capsular transparency was higher than in Group 3 (P < .04). Central opacification percentage was lower in Group 1 than in Groups 2 and 3 (P < .04). These authors concluded that capsulorhexis with a slightly smaller diameter than the IOL optic appears to be better than a large-size capsulorhexis in reducing the incidence of PCO.

Akahoshi has reported his experience of three-piece AcrySof" IOL implantation in more than 17,000 human eyes in Japan. The incidence of YAG capsulotomy has been found to be 1.19% (207 of 17,329) after 75 months of follow up period. Among the cases treated with Nd: YAG laser, 81.2% had an eccentric and incomplete coverage of the lens optic by the anterior capsulorhexis margin. In 8.2% of the cases, the anterior capsule margin was on the optic edge and in 10.6% of the cases it was completely outside. Longterm follow up revealed that the incidence of after cataract formation in three-piece AcrySof" IOLs was extremely low. The size and position of the CCC, however, seems to be one of the most important factors in reducing the YAG capsulotomy rate. (T. Akahoshi, Clear corneal cataract surgery and AcrySof" implantation. Presented in the ASCRS Symposium on Cataract, IOL and Refractive Surgery, Boston, MA, April 28, 2001).

  Pharmacological Prevention of Posterior Capsule Opacification Top

Intraocular application of pharmacologic agents has also been investigated by several authors as a means to prevent PCO. [56],[57],[58],[59],[60],[61] The idea was to selectively destroy the LECs and avoid toxic side effects on other intraocular tissues such as the sensitive corneal endothelium. Pharmacologic agents being investigated include antimetabolites (such as methotraxate, mitomycin, daunomycin, 5-FU, colchicine, and daunorubicin), anti-inflammatory substances, hypo-osmolar drugs, and immunological agents.

We designed an intracapsular ring to prevent capsular bag contraction and also to inhibit LECs proliferation and metaplasia by sustained release of 5-FU. [62],[63],[64] The effects of the intracapsular ring on the prevention of PCO was prospectively studied by analysing postmortem ocular specimens macroscopically (using the Miyake-Apple technique[65],[66]) and histologically. We also evaluated the toxic effects of 5-FU on the corneal endothelium, capsular bag and retina of rabbits.[62] Results of this study suggested that implantation of intracapsular ring may prevent central PCO after cataract surgery by mechanically blocking migration of lens epithelial cells towards the central visual axis. The potential pharmacological effect of 5-FU for PCO prevention was not demonstrated in this experimental study.[62]

Toxicity to corneal endothelium and other ocular structures remains one of the major concerns for using cancer chemotherapeutic drugs, anti-inflammatory substances, hypo-osmolar drugs, and immunological agents, when the intralenticular compartment is in direct contact with the anterior chamber. However, with the development of a Sealed Capsular Irrigation (SCI) device , it is now possible to precisely deliver the pharmacological/ hypo-osmolar agents to the lens epithelial cells within the capsular bag, while minimising the potential for collateral ocular damage.[34],[35]

Sealed capsule irrigation of maintaining postoperative capsular bag transparency

A Sealed Capsule Irrigation device may allow the isolated safe delivery of pharmacologic agents into the capsular bag following cataract surgery [Figure - 10].[34],[35] Developed by one of the authors (AJM), SCI is a type of sealed irrigation system applied to the internal eye. In the eye, the technique of capsular bag irrigation may be used with pharmacologic agents to target LECs, eliminate PCO and help maintain capsular bag transparency. We consider that SCI should meet the following requirements: it should be minimally invasive; be easy to use; fit through a small incision; be relatively inexpensive; provide a repeatable seal with the lens capsule; and not add significantly to the duration of routine cataract surgery.

The intact human lens capsule is functionally a separate compartment within the eye. Once breached, the intralenticular compartment becomes continuous with the anterior chamber and the rest of the eye. Since an intact capsulorhexis is now routinely performed, we devised a technique to reseal the capsular bag following lens removal. By resealing the capsular bag, we recompartmentalise the lens and allow for selective irrigation of the internal contents of the capsular bag.

The SCI device called Perfect Capsule' (Milvella, Sydney, Australia), made from biomedical grade soft silicone, allows the surgeon to reseal the capsular bag. The device consists of a rounded plate containing a suction ring which abuts the anterior capsule, and an extension arm that passes through a phacoemulsification wound. This extension arm carries a vacuum channel which supplies vacuum to the suction ring, and a combined irrigation and aspiration channel. The irrigation and aspiration channels allow for communication between the sealed capsular bag and the external eye.

We have tested a first generation device on post-mortem porcine lens capsules and demonstrated its effectiveness for sealed capsule irrigation.[34] We have further refined the device to its current third generation form, to incorporate changes which would allow it to be used in small incision cataract surgery, and address the potential risk of pseudosuction, which would result in loss of sealing of the capsular bag. We considered the adult capsule to be less elastic than the paediatric capsule, and less prone to pseudosuction. The device was modified to contain a vacuum manifold within the suction ring such that ensures no focal occlusion of the suction ring is not possible at any point, and that the vacuum is evenly distributed to the entire ring.

To validate this third generation device, 13 randomly chosen devices were subjected to testing on a pig capsule. In all cases, the devices sealed the capsule using vacuum generated by a 20mL lockable syringe resulting in a maximal vacuum pressure of greater than 700mmHg on application, with no evidence of pseudosuction with less than 2.5% reduction in vacuum pressure over a one-minute period. One of these devices was then selected for repeat testing for a period of 10 minutes with less than 5% reduction in vacuum at 10 minutes. The technique of SCI has also been performed with the third generation device in 12 human eyes, using trypan blue to irrigate the capsular bag. In all subjects, there was no visible leakage of trypan blue into the anterior chamber following SCI [Figure - 11].[34]

In a study on rabbits, we have been able to selectively irrigate the capsular bag with mitomycin 0.02% with an exposure time of one minute, without adverse damage to any intraocular structure. Ordinarily, exposure of the internal rabbit eye to mitomycin 0.02% will lead to significant toxicity to the retina and cornea, but this did not occur when SCI was performed.[34]

We are continuing to demonstrate that selective capsular bag irrigation can be performed in animals and humans. Using this technique, lens epithelial cells can be safely targeted to prevent PCO using precise delivery of known doses of pharmacologic agents, with less fear of toxicity to surrounding intraocular structures. This method may be utilised to eliminate or modulate LEC activity after cataract surgery. This may lead to less postoperative inflammation and a theoretical reduction in the risk of postoperative cystoid macular oedema, reduced anterior and posterior capsule opacification, and allow for definitive implantation of multifocal and accommodative lenses so that the treatment of presbyopia may finally become a reality. Clinical studies will be needed to test efficacy of SCI during paediatric cataract surgery. Theoretically, SCI may be helpful to eliminate of LECs and therefore avoid the PCO/secondary membrane formation postoperatively. It may obviate the need for primary posterior capsulotomy with anterior vitrectomy intraoperatively.

There are many potentially beneficial agents which may be used with SCI. PCO modulation may be effected by apoptosis or deactivation of lens epithelial cells rather than cell death or destruction.

  Conclusion Top

The tools, surgical procedures, skills, and appropriate IOLs are now available to significantly reduce PCO. A major reduction of Nd: YAG laser capsulotomy rates towards single digits is now possible- because of application of aforementioned surgical factors and factors related to the modern lens designs and the biomaterials. This will obviously be of great benefit to the patients in achieving improved longterm results and in avoiding of Nd: YAG laser capsulotomy related complications. Whole one cannot precisely determine the relative proportion or contribution of the IOL design vs the surgical techniques to the decrease of Nd: YAG laser rates, this could be possible with continuing analysis including annual updates and increasing numbers of pseudophakic autopsy eyes

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]

  [Table - 1], [Table - 2]

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De Iongh, R.U., Wederell, E., Lovicu, F.J., McAvoy, J.W.
Cells Tissues Organs. 2005; 179(1-2): 43-55


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