Life 4°C Versus Optisol in Corneal Storage Media
Condition: Complications of Corneal Transplant
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare the success of storing a donor cornea in Optisol GS,
      the current standard vs. storing the donor cornea in Life4°C, a newer solution. The donor
      cornea to be used for EK will be provided by an eye bank and will have been stored in either
      an Optisol GS solution or a Life 4°C solution. At 6 months, the doctors will determine
      whether there are any comparable differences in cell loss and graft clarity between the two
      donor corneas.
    

Detailed description: 
      1. Purpose/ Specific Aims

           The purpose of this study is to compare the success of storing a donor cornea in Optisol
           GS, the current standard solution that the donor cornea is stored in prior to surgery
           versus storing the donor cornea in Life 4°C, a newer solution. Laboratory tests that led
           to the recent approval of this new storage solution by the Food and Drug Administration
           have suggested that this solution may support the health of the endothelial cells better
           than Optisol GS. While there is extensive in vitro and ex vivo data regarding Life 4°C
           and its transport chamber, there are no short or long term in vivo studies to examine
           its performance clinically and the relationship of its performance to Optisol GS and its
           transport chamber. This study has been designed to examine these questions.

           1.1 STUDY OBJECTIVES Primary objective: To determine whether endothelial cell loss post
           EK is comparable 6 months postoperatively for donor corneas preserved in Life 4°C vs.
           Optisol GS corneal storage media

           Secondary objective: To determine whether graft clarity post EK is comparable 6 months
           postoperatively for donor corneas preserved in Life 4°C versus Optisol GS corneal
           storage media

        2. Background and Significance

      Currently it is estimated by the Eye Bank Association of America (EBAA) that 3500 to 5000
      Americans wait an average of 1-2 months to undergo penetrating or endothelial keratoplasty.
      The situation worldwide is considerably more complex, and the availability of tissue is much
      more limited. In view of this shortage of tissue, much research has been undertaken with a
      view towards prolonging donor storage time and yet maintaining a viable endothelium, which is
      crucial to successful transplantation. Extended preservation time has transformed corneal
      transplantation surgery into an elective procedure and has facilitated the availability of
      available donor tissue. However, corneal preservation involves many other factors in addition
      to simply increasing the length of donor storage time.

      The functional status of the endothelium, epithelium and sustained corneal deturgescence
      after corneal preservation are of great clinical importance and contribute primarily to the
      success of the surgical outcome. Other areas of concern to be addressed in the development of
      a complete corneal preservation medium include the enhancement of corneal wound healing and
      the reduction or elimination of the normal progressive loss of endothelial cells post
      keratoplasty. Preservation of existing endothelial cells during corneal preservation is
      important because endothelial cells continue to be lost after penetrating keratoplasty at a
      faster rate than normal aging1. Timely and adequate healing of corneal tissues is required to
      restore visual acuity.

      The current "gold standard" in 4°C corneal preservation medium is Optisol GS (Bausch & Lomb
      Surgical, Inc.). This is an improved formulation of Optisol 2 (Chiron Vision, Irvine, CA,
      U.S.A.) modified by the addition of 200 µg/ml of streptomycin sulfate. Optisol preserved the
      corneal endothelium as well as DexSol (Chiron Vision, Irvine, CA, U.S.A.), the previous
      widely used corneal preservation medium, and was better at preventing stromal swelling during
      storage 2-5. The addition of streptomycin to gentamicin in corneal preservation media was
      effective against resistant strains of bacteria6. Optisol GS exhibited improved antibacterial
      activity without any increased toxicity to the endothelium7-8. In vitro studies of Optisol GS
      stored human corneas concluded that storage time at 4°C is limited by the inability to
      preserve corneal epithelium greater than 1 week, although 84% of the endothelium was deemed
      viable after three weeks of storage 9,10. A clinical study found that the probability of an
      epithelial defect 1 day after penetrating keratoplasty increased with increased storage time
      in Optisol GS11.

      Optisol GS is a chondroitin sulfate containing medium supplemented with dextran, additional
      antioxidants, energy sources and nutritive substrates12. These components address the
      understanding that the cornea is still metabolically active at low storage temperatures. The
      composition of synthetic media must address the increased stromal hydration that occurs with
      increased preservation time and reduced temperatures. In the progression of intermediate-term
      corneal preservation medium development, dextran, an osmotic agent, was added in an effort to
      reduce the intraoperative rebound swelling associated with chondroitin sulfate containing
      medium. Chondroitin sulfate and dextran assist in the prevention of stromal hydration by
      increasing the colloidal osmotic pressure in the aqueous environment surrounding the stored
      cornea. Sustained corneal deturgescence during and after corneal preservation are of great
      clinical importance, reducing handling and suturing problems encountered by the transplant
      surgeon, thus reducing the risk of graft failure

      A superior corneal preservation medium would maintain cellular viability while lengthening
      current storage times for more efficient use of donor tissue, prevent stromal swelling to
      facilitate keratoplasty, and eliminate or suppress microbiologic growth to prevent rare but
      catastrophic endophthalmitis.

      2.1 INVESTIGATIONAL AGENT Life 4°C is an FDA approved, new advanced corneal preservation
      medium (30 ml) for storage of human corneas suitable for keratoplasty for up to 14 days under
      refrigeration (2-8°C). Life 4°C is sterile, non-pyrogenic, advanced buffered corneal
      preservation medium which is supplemented with chondroitin sulfate (membrane stabilizer),
      recombinant human insulin (cell metabolism enhancer), Dextran (osmotic agent), glutathione
      (antioxidant, free-radical scavenger, enzyme cofactor), stabilized L-glutamine, ATP
      precursors, nutrient cell supplements, amino acids, vitamins, trace elements, gentamycin,
      streptomycin and phenol red (pH indicator). Life 4°C has been formulated to be used to the
      full extent of corneal storage time, by preventing stromal swelling, maintaining corneal
      epithelium and providing optimum endothelial cell preservation.

      In addition, TRANSEND is a new corneal storage, viewing and transport system. It was designed
      for performance to meet the challenges of extended storage, specular microscopy and shipping.
      TRANSEND viewing chamber is designed to accommodate larger scleral rims needed for the newest
      surgical procedures. The increased medium volume (30 ml) and greater fluid flow to the cornea
      reduces metabolic waste build-up, important to cellular health. Increased medium volume
      results in excellent corneal preservation with minimal corneal swelling during storage. The
      TRANSEND viewing chamber utilizes both a top seal and o-ring side seal for leak-proof
      performance. The cornea is held securely during storage, specular microscopy and shipping.
      The viewing chamber is gamma irradiated, therefore there are no ETO residuals. The use of new
      tamper seals eliminates the use of high temperature heat seals. The outer shipping container
      allows the inner viewing chamber to arrive dry and secure to the surgeon.
    

Intervention name(s): Corneal donor storage in Optisol GS media solution; Life 4°C solution for cornea storage
Intervention type(s): Other; Other
Intervention description(s): Donor tissue is preserved in the Optisol media until ready for implantation; Donor cornea is stored in the Life 4°C media prior to implantation.
Other intervention name(s): Chondroitin Sulfates; Dextrans; Gentamicins; Complex Mixtures; Culture Media, Serum Free; Chondroitin Sulfates; Dextrans; Gentamicins; Streptomicins; Complex Mixtures; Culture Media, Serum Free
Intervention MeSH terms: Gentamicins; Dextrans; Pharmaceutical Solutions
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Other
Keywords: endothelial keratoplasty