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EyeWorld - CATARACT - Preventing PCO
        F EBRUARY 2011
             CATARACT/                Preventing PCO
                    IOL
                                      by David Spalton, F.R.C.S.
                                      ESCRS Ridley Medalist David Spalton, F.R.C.S.,
                                      St. Thomas Hospital, London, discusses current
                                      and future methods of PCO prevention
                                      Two or 3 years ago,
          Despite
                                      people thought that
          advances in IOL             posterior capsular
          design and                  opacification (PCO) had
          surgical
                                      become a thing of the
          technique,
          posterior                   past. Although it's less of
          capsule                     a problem now, it's still a
                                                                    Cellular PCO Source:
          opacification               significant clinical issue,
          (PCO) continues                                           Mostafa A. Elgohary, M.D.
                                      especially with regard to
          to be a problem
          for cataract                the use of premium
          surgeons.                   lenses and
          Although the
                                      accommodative lenses.
          YAG laser is an
                                      PCO is one of the limiting
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          easy,                       factors in the use of
          "miraculous" fix
                                      these lenses. Patients
          for patients with
          PCO, the rare               with diffractive multifocal
          creation of a               lenses are susceptible to
          retinal tear or             very small amounts of
          detachment and
                                      PCO. Diffractive lenses
          the potential for
          permanent post-             divide the light into two
          YAG floaters                foci, which means there's
                                                                    Fibrotic PCO Source:
          makes its use
                                      only about 40% of light
          less than ideal.                                          Mostafa A. Elgohary, M.D.
          A treatment that            in each focus; therefore,
          could eliminate             the patient needs all the light he or she can get. A
          PCO would help              bit of PCO knocks that down considerably.
          improve surgical
          outcomes and                It's a problem for accommodative lenses as well
          improve the
                                      because when the bag fibroses, it seems to stop
          chances of one
          day achieving               the lenses from moving. Of course you can't refill
          an injectable               the capsular bag with an elastic polymer because
          crystalline lens
                                      it develops PCO, too.
          substitute that
          could restore
                                      Lens design and surgical methods
          accommodation.
                                      At the moment, PCO is a multifactorial problem.
          In this month's
          column, David               In order to prevent PCO, changes in IOL material
          Spalton,                    and design as well as various surgical techniques
          F.R.C.S., reviews
                                      and pharmacological methods to remove or
          some of the
          issues and
                                      destroy lens epithelial cells have been prescribed.
          research that               A lens with a good, sharp square-edge profile is
          are ongoing in              necessary to prevent PCO. My colleagues and I
          regard to
                                      looked at the electromicroscopy of a lot of IOLs,
          reducing or
          potentially                 and we saw that the edge profile varies. Some
          eliminating the             manufacturers make good ones while others
          occurrence of               don't. That's an important point because some
          PCO.
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          Richard                     lenses may be advertised as having a square-edge
          Hoffman, M.D.
                                      profile, but they're not all equally effective.
          Column Editor
                                      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
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                                      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.
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                                      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
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                                      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
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                                      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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