PCO still a major hurdle in successful cataract surgery

Despite advances that have increased the success and safety of cataract surgery in recent years, posterior capsule opacification remains a common complication.

Understanding the complex mechanism that leads to PCO has been the ambition of many studies, but every step forward seems to move the goal farther away, as potential new factors for PCO pathogenesis are uncovered.

Preventing “after-cataract” reactions is a strenuous fight against nature because lens epithelial cell (LEC) migration and transdifferentiation are nature’s back-up strategies to the loss of lens tissue.

According to Kerry D. Solomon, MD, OSN Refractive Surgery Board Member, investigation of a full 360° barrier on the edge of the optic led to the discovery that a square-edge design might be preferred for delaying the migration of LECs.

“What we learned is that a square-edge design on that laser ridge did slow down or delay the migration, and that carried over to the design of lens optics,” Dr. Solomon said. “The more square of an edge and the more defined of an edge, the better the delay or the better the barrier.”

Even though surgeons are thorough at cataract surgery, it may be impossible to remove every lens cell at the cellular level, according to Kerry D. Solomon, MD. Image: David Cook Photography

In the case of a full peripheral ring barrier, there was no compression of the posterior optic, and ultimately, cells that moved beyond the barrier had ample space to proliferate, Dr. Solomon said.

Just as a square-edge design causes the optic to place more pressure on the posterior capsule, having a posterior convex surface will also help to push against the capsule, he said. In addition, Dr. Solomon recommended angulated haptics to push the optic to the bag.

While these strategies often prevent the initial migration of cells, the late onset of Soemmering’s ring formation may lead to an abolished capsular bend and subsequent proliferation of LECs.

The formation of Soemmering’s ring 3 years to 5 years after surgery can be observed in patients with iris coloboma.

“It starts forming in the periphery, and it disrupts centripetally the collagenous sealing of both capsular leaves along the optic rim,” Rupert Menapace, MD, OSN Europe Edition Editorial Board Member, said.

This secondary barrier failure may take up to 7 years to 9 years to occur, and eventually the barrier effect of capsular bending is abolished, he said.

Although acrylic material has excellent characteristics, the ideal IOL for PCO prevention is a silicone square-edge three-piece IOL with a thin optic-haptic junction. Broad-based haptics, such as those used in one-piece IOLs, inevitably disrupt the barrier at the optic insertion, Dr. Menapace said.

PCO development

“Following cataract surgery with IOL implantation, the equatorial lens epithelial cells, which reside in the equator of the capsular bag, try to produce new lens fibers to build up a new lens. This regeneratory PCO is essentially Elschnig pearls that migrate to the posterior capsule behind the IOL optic, causing secondary opacification and vision loss,” Oliver Findl, MD, said.

A second subpopulation of LECs resides under the anterior capsule and, in the healthy eye, provides nutrition to the crystalline lens. After cataract removal, these LECs undergo transdifferentiation into myofibroblasts and lay down collagen that causes anterior capsule whitening and capsule contraction that could lead to decentration and tilting of the lens.

Oliver Findl

“Both of them, we don’t want — the regeneratory type and the fibrotic type of after-cataract,” Dr. Findl said.

Regeneratory PCO occurs in two waves. The first is shortly after surgery and leads to the formation of a monolayer of regenerating LECs on the posterior capsule. While unperceived with standard monofocal lenses, this thin opaque layer can cause further reduction of contrast sensitivity, glare and waxy vision with multifocal IOLs, Dr. Findl said.

The second wave typically occurs 12 months to 18 months after surgery, leading to Elschnig pearl formation on the posterior capsule. This late formation is visually disturbing with all lenses.

PCO delay

While different methods of digital imaging and automated analysis are used to quantify PCO in clinical studies, in standard clinical practice, the incidence of PCO is measured with YAG rate. This is not an effective indicator, according to Dr. Findl, because it depends on a variety of factors, including patient demand, symptoms and awareness of symptoms. In addition, the physician’s decision to perform the procedure is also a factor.

YAG rate has significantly decreased in the past 15 years. Literature in the 1990s reported a 30% to 40% rate at 3 years, while the current rate is between 3% and 10%, thanks to modern surgical techniques and sharp-edge lenses.

However, beyond the 3-year time frame, YAG rates show a significant increase.

“The follow-up of long-term trials shows that even those who have very little PCO at 3 years will develop it over the next 2 years, and at 8 to 10 years, capsulotomy rate is indeed very high. At some point, most patients, if they live long enough, develop PCO and have YAG capsulotomy,” Dr. Findl said.

“It seems that we have been able to delay PCO rather than eradicate it,” Dr. Menapace said.

Rupert Menapace

Dr. Menapace noted that there are distinctions to make regarding PCO. Lens design, namely square edge vs. round edge, has been shown to make a difference during the early years, with lens material playing a role in the long term.

A 10-year retrospective comparison study of sharp-edge hydrophobic acrylic IOLs and round-edge silicone IOLs demonstrated that time plays a factor in favor of silicone. At 10 years, acrylic lenses had a YAG rate of 42%, while silicone lenses, even though they had round edges, had a YAG rate of 18%.

The study was carried out at the University Hospital of Vienna, with the contribution of both Dr. Menapace and Dr. Findl. It is a public hospital, and no commercial interests were involved.

“In other studies comparing sharp-edge silicone and acrylic IOLs, we demonstrated that they both do well up to 3 years. Then, acrylic lenses lose ground, as their capsulotomy rate rises sharply after 3 to 5 years,” Dr. Menapace said.

An intraindividual comparison of the same acrylic lens with round edges and sharp edges showed that, in the first 5 years, the sharp edge did significantly better. Then, between 5 years and 8 years, the curve of the sharp edge rolled back and approached the curve of the round edge, meeting it at the same point at 8 years.

“This late onset of PCO with sharp-edge acrylic lenses is due to what we call ‘secondary barrier failure,’” Dr. Menapace explained.

Surgical maneuvers

There are other prerequisites that are needed to create a long-lasting barrier effect.

“One of the most critical points to prevent PCO is to perform a regular, round, well-centered capsulorrhexis, overlapping the IOL optic over 360°. Wherever there is no overlap, there is no bending and LECs can migrate posteriorly,” Dr. Findl said.

A thorough cortical clean-up is also mandatory because any remnants of cortical material are a substrate for Soemmering’s ring formation.

“In addition to [irrigation and aspiration] to remove residual cortical material at the end of surgery, I use a 30-gauge cannula and [balanced salt solution] for jet-polishing the equator and posterior capsule, blowing away any adherent remnants of cortical matters and lens epithelial cells,” he explained.

Most surgeons now agree that the anterior capsule should not be cleaned because anterior LECs are essential to create and maintain capsule fusion around the IOL optic.

“When in contact with the IOL optic, they transdifferentiate into myofibroblasts, which create a deposit of collagen, gluing together the two capsule leaves along the fusion line. The integrity of the anterior LEC layer is necessary to create and preserve the barrier effect,” Dr. Findl said.

In order to create a second line of defense against PCO, Dr. Menapace developed his own technique of posterior capsulorrhexis with posterior optic buttonholing. The technique entails the performance of a 4.5-mm posterior capsulorrhexis and buttonholing a three-piece IOL behind it. The IOL forms a tight diaphragm with the posterior capsule, preventing LECs from gaining access to the retrolental space.

“I now have over 1,000 cases implanted with this technique with a mean follow-up approaching 5 years, and it’s up to 7 years in some cases. Efficacy is 100%. We have had no case of lens epithelial cell migration onto the optic inside the rhexis edges,” Dr. Menapace said.

Concerns have been raised about a potential increase in retinal detachment rate, but the lower-than-average 0.1% retinal detachment rate in Dr. Menapace’s series seems to indicate that posterior optic buttonholing not only is safe in this respect, but even has a protective effect against retinal complications. It may be that the location of the lens optic, approximately 1 mm more posterior than in standard in-the-bag implantation, may stabilize the vitreous better, counteracting posterior vitreous detachment.

Crossing the barrier

Despite the use of square-edge IOLs and appropriate surgical techniques, PCO still occurs.

“Most surgeons do a good job today of cleaning up most of the remnants of cortex and LECs during the primary surgery,” Dr. Solomon said. “[But] it is really impossible to remove every lens cell at the cellular level.”

Dr. Solomon said that a few materials, such as sterile water and chemotherapeutic agents, have been shown to eliminate all LECs; however, these therapies have not been seriously pursued, as the substances could potentially leak out of the capsular bag and into the eye.

Another possible cause of PCO could be the vast variation among lenses, according to Liliana Werner, MD, PhD. Dr. Werner and colleagues devoted recent research to the interaction between ocular tissues and IOL designs and materials. The researchers found a large deviation from a perfect square in all but 13 types of examined lenses.

“Square edge is the most important design feature for PCO prevention, at least in the short term,” Dr. Werner said.

The same studies showed that lens material has little influence. Dr. Werner found that hydrophilic lenses tend to fail as a barrier because they have much rounder edges as a group. Hydrophobic acrylic and silicone do equally well, but it is important that the square edge be present around 360°.

There are also other features related to capsule morphology after IOL insertion that likely play a role in the occurrence and prevention of after-cataract.

“An open and expanded capsular bag retains transparency, as shown by studies in eyes implanted with disc-shaped or dual-optic IOLs,” Dr. Werner said.

This is probably due to different mechanisms, including the well-known concept of “no space, no cells.” If the capsular bag is filled completely, then there is no space for the cells to grow. Furthermore, the capsular bag under stretch or mechanical compression may result in inhibition of LEC metaplasia, migration and proliferation.

“Also, in an open capsular bag, there is a constant irrigation of the inner compartment by aqueous humor. Finally, the separation between the anterior capsule and the optic may play a role in preventing anterior capsule opacification,” Dr. Werner said.

Future IOL possibilities

There are IOLs, old and new, that share some or all of these characteristics. Most are experimental prototypes. The goal is to imitate as closely as possible the natural lens and recreate a pre-cataract situation in the capsular bag.

Among disc-shaped IOLs, the Concept 360 (Cornéal Laboratoires), designed by Philippe Sourdille, MD, OSN Europe Edition Editorial Board Member, created an all-round barrier effect at the equator to maintain a safe distance between the anterior capsule and the optic. The weak point of the IOL was its dependency on the capsular bag diameter. The six haptic components came perfectly into contact in eyes of appropriate size, but were too loose in larger eyes, and LECs could migrate through the gaps. The lens is not currently available.

Another prototype is a disc-shaped IOL developed by Anew Optics. The optic is suspended between two complete haptic rings connected by a pillar of haptic material. It maintains the capsular bag open and the anterior capsule at a distance from the anterior optic surface.

A dual-optic concept was also introduced by Okihiro Nishi, MD. Two square-edge IOLs are implanted, one posteriorly and one anteriorly in the capsular bag, to seal the anterior and posterior capsulorrhexis. Silicone polymer is injected between them, through a hole in the anterior lens.

“It is convex so that it will push against the capsule, and because it [consists of] two optics, it is really going to fill up a larger portion of the capsular bag, and the square edge should slow down the delivery of PCO,” Dr. Solomon said.

Another research direction has been pursued by Marie-José Tassignon, MD, with a “bag in the lens” IOL design and implantation technique. Both the anterior and posterior rhexes are positioned inside a fine groove surrounding the optic of a specifically designed lens, creating a stable barrier against cell migration. – by Michela Cimberle and Michelle Pagnani

Are safety concerns regarding MICS lenses and PCO justified?

Lindstrom's Perspective
Posterior capsular opacity remains major unmet need in cataract surgery

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• Oliver Findl, MD, is chair of the Department of Ophthalmology, Hanusch Hospital, Vienna, and Consultant Ophthalmic Surgeon at Moorfields Eye Hospital, London. He is also the founder and chair of Vienna Institute for Research in Ocular Surgery. He can be reached at oliver@findl.at.
• Rupert Menapace, MD, is head of the Cataract & Intraocular Lens Service, University of Vienna Medical School. He can be reached at the Medical University of Vienna, Vienna General Hospital, Department of Ophthalmology, Waehringer Guertel 18-20, A-1090 Vienna, Austria; 43-1-404007941; fax 43-1-404006630; email: rupert.menapace@meduniwien.ac.at.
• Kerry D. Solomon, MD, can be reached at Carolina Eyecare Physicians, 1280 Johnnie Dodds Blvd., Suite 100, Mount Pleasant, SC 29464; 843-881-3937; fax: 843-884-8587; email: kerry.solomon@carolinaeyecare.com.
• Liliana Werner, MD, PhD, is an associate professor at the John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, UT 84132; 801-581-6586; fax: 801-581-3357; email: liliana.werner@hsc.utah.edu.
• Disclosures: Drs. Findl and Menapace have no direct financial interest in the products discussed in this article, nor are they paid consultants for any companies mentioned. Dr. Solomon is a consultant for Alcon, AMO and Bausch + Lomb. Dr. Werner is a consultant for PowerVision and Visiogen/AMO and performs contract research studies for Anew Optics.