February 2011

 

CATARACT/ IOL

 

Preventing PCO


by David Spalton, F.R.C.S.

 

Despite advances in IOL design and surgical technique, posterior capsule opacification (PCO) continues to be a problem for cataract surgeons. Although the YAG laser is an easy, "miraculous" fix for patients with PCO, the rare creation of a retinal tear or detachment and the potential for permanent post-YAG floaters makes its use less than ideal. A treatment that could eliminate PCO would help improve surgical outcomes and improve the chances of one day achieving an injectable crystalline lens substitute that could restore accommodation.

In this month's column, David Spalton, F.R.C.S., reviews some of the issues and research that are ongoing in regard to reducing or potentially eliminating the occurrence of PCO.

Richard Hoffman, M.D. Column Editor

 

ESCRS Ridley Medalist David Spalton, F.R.C.S., St. Thomas Hospital, London, discusses current and future methods of PCO prevention

Cellular PCO Source: Mostafa A. Elgohary, M.D.

Fibrotic PCO Source: Mostafa A. Elgohary, M.D.

Two or 3 years ago, people thought that posterior capsular opacification (PCO) had become a thing of the past. Although it's less of a problem now, it's still a significant clinical issue, especially with regard to the use of premium lenses and accommodative lenses. PCO is one of the limiting factors in the use of these lenses. Patients with diffractive multifocal lenses are susceptible to very small amounts of PCO. Diffractive lenses divide the light into two foci, which means there's only about 40% of light in each focus; therefore, the patient needs all the light he or she can get. A bit of PCO knocks that down considerably.

It's a problem for accommodative lenses as well because when the bag fibroses, it seems to stop the lenses from moving. Of course you can't refill the capsular bag with an elastic polymer because it develops PCO, too.

Lens design and surgical methods

At the moment, PCO is a multifactorial problem. In order to prevent PCO, changes in IOL material and design as well as various surgical techniques and pharmacological methods to remove or destroy lens epithelial cells have been prescribed. A lens with a good, sharp square-edge profile is necessary to prevent PCO. My colleagues and I looked at the electromicroscopy of a lot of IOLs, and we saw that the edge profile varies. Some manufacturers make good ones while others don't. That's an important point because some lenses may be advertised as having a square-edge profile, but they're not all equally effective. Hydrophylic lenses have a poorer square-edge profile than those made of hydrophobic materials. We developed a technique to look at square edges with what's called environmental scanning microscopy. You can look at a wet specimen in an electromicroscope in its natural state. We could image these lenses very clearly and measure the sharpness of the edge using dedicated software we developed.

Another factor that's important in PCO prevention is having a 360-degree square edge barrier right around the optic. A lot of lens designs have a break in the barrier at the optic haptic junction and that allows cells to escape onto the posterior capsule. Everything in IOL design is a balance of the pros and cons. If we're going to have a 360-degree square edge, it tends to mean the lens has to be slightly thicker, and that means we can't get it through as small of an incision size. On the other hand, if we want a lens for a very small incision, the downside is we tend to get higher PCO. In terms of surgical methods of PCO prevention, making the capsulorhexis slightly smaller than the optic of the implant is important. Over 2-4 weeks after surgery, the capsule fibroses and that fibrosis pushes the lens back onto the posterior capsule and creates a mechanical barrier on the posterior edge of the lens where the square edge barrier is located. It forms a sort of pressure barrier to the migration of epithelial cells. In addition, if the rhexis is asymmetrical or off of the lens implant, we don't get the same efficacy in pushing the lens back against the posterior capsule.

Dealing with lens epithelial cells

There are also pharmacological methods of dealing with PCO, although fundamental problems have been associated with many of them. One of the concepts involves locking up the lens epithelial cells in the equatorial capsule. The surgeon performs a posterior capsulorhexis and prolapses the optic through that or uses what's called the bag-in-the-lens, a Belgian-designed lens. The rhexis has to be 5 mm in diameter, it has to be central, and there must be a concentric posterior capsulorhexis. The lens is placed so that both anterior and posterior rhexes lie in this groove in the lens, and these eyes maintain an entirely clear posterior capsule because there is no posterior capsule. However, a recent report by Liliana Werner, M.D., Ph.D., research associate professor, ophthalmology and visual sciences department, John A. Moran Eye Center, University of Utah, Salt Lake City, showed these go on to develop massive Soemmering's ring. While the posterior capsule is clear, there's a downside, so this is not the answer to PCO prevention.

Another concept concerns the killing of all the epithelial cells in the capsular bag using a device called the Perfect Capsule (Milvella, North Sydney, Australia), which is held over the capsulorhexis by a suction ring in the eye at the time of surgery. The inside of the capsular bag is isolated and then irrigated with a solution to kill the lens epithelial cells. Once again, although it sounds like a good concept, clinical studies have been rather disappointing. The lens epithelial cells are probably protected by remnants of overlying hydrophilic cortical material so things like aqueous solutions can't penetrate. Two years after surgery, these eyes have the same amount of PCO as the control eyes.

The idea of removing all of the cells from the bag has also been explored using a variety of instruments and techniques. The problem here is that we have to remove the equatorial cells. If we just remove the anterior capsule cells, the eyes get more PCO. The reason for this is we reduce the fibrosis in the anterior capsule so we restrict the fibrosing force within the capsular bag. This means we don't push the lens implant against the posterior capsule as tightly as we would with a fibrosed posterior capsule, so cells can get in and cause PCO. The A.R.C. Laser (Nuremburg, Germany) is a new device developed for cell removal. It uses laser shockwaves, and we can blast all the cells off the capsule, so we end up with a capsule that is acellular as long as we can go around for 360 degrees and treat it all. It also seems to remove adhesion molecules. The technology sounds quite promising and clinical trials are ongoing in Germany at the moment. In theory, though, the problem with this focal laser treatment is if we miss a few cells, PCO could develop. Another problem is we don't know if there's any danger that the laser shockwaves could damage the iris or the ciliary body.

In Britain, my colleagues and I recently tested this cell removal idea by taking human post-mortem capsular bags and growing them in a new laboratory cultured model. It's the best model that has been described so far and involves performing surgery on a human post- mortem lens and growing it in an incubator for weeks following the operation. What we showed was if we take a pair of eyes from the same patient, do the surgery, put an IOL in each eye, and kill all the lens epithelial cells in the fellow eye, 3 or 4 weeks post-op, we would see that in the control eye, the IOL is fibrosing into the bag, just as in a human eye. In the treated eye, however, the lens wobbled. This indicated that with the current lens design, we need lens epithelial cells there to fix and stabilize the IOL. If we are going to kill all the cells in the bag, we have to radically change the design of the lens implant. There are some fundamental questions there, and no one knows what the long-term consequences of killing all the cells in the human eye are. Do we need the cell bed to maintain the collagen and the elasticity of the bag? Does removing these cells ultimately cause degeneration of the capsular bag?

New ideas

Open-bag devices are a novel idea. Studies on the Synchrony lens (Abbott Medical Optics, Santa Ana, Calif.) have reported very low rates of PCO. It seems there's a possibility that by keeping the capsular bag open after surgery and allowing circulation of aqueous into the capsular bag, we may be removing cytokines and growth factors and therefore we don't stimulate the lens epithelial cells to proliferate in the same way. There are a number of companies that are involved in making such devices, although it's entirely experimental at this point. We will also have to see whether the Synchrony lens, when it comes into standard clinical practice, continues to have low PCO rates when it's being used by a lot of surgeons. With the other three approaches to dealing with lens epithelial cells all having fundamental problems, the idea of opening the capsular bag is different and worth exploring.

Editors' note: Dr. Spalton has no financial interests related to his comments.

Contact information

Spalton: +44 020 7935 6174, practice_manager2@davidspalton.com

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