Ординатура / Офтальмология / Английские материалы / Corneal Endothelial Transplant (DSAEK, DMEK & DLEK)_John_2010

Introduction

The first experiments on keratoplasty took place in the early 19th century, with Franz Reisinger attempting to suture corneal grafts after excising host corneal tissue in rabbits (See also Chapter 14, History of Lamellar and Penetrating Keratoplasty). The experiments failed and the grafts were rejected; it would be decades until the first successful human keratoplasty procedure was performed. The procedure has evolved dramatically since the first successful keratoplasty, and today an expert corneal surgeon can perform a penetrating keratoplasty (PKP) in less than 30 minutes, significantly improve the preoperative visual acuity, and try to protect against corneal graft rejection with local steroid eyedrops. However, the procedure is far from being perfect; a host of autoimmune diseases and chemical injuries that cause corneal scarring, have a high rate of corneal graft rejection after a PKP. Furthermore, the PKP procedure requires corneal sutures, with the potential of poor wound healing, irregular astigmatism, and suture-induced corneal neovascularization leading to potential graft rejection and vision loss. Since the entire cornea is removed during a PKP procedure, there is a risk of intraoperative expulsive hemorrhage, with possible loss of the eye. Advances in keratoplasty research have focused on improving the surgical techniques to reduce these risks.

The formation of eye banks for providing donor corneal tissues for keratoplasty procedures, has been a huge step forwards in the field of corneal transplantation. The first successful corneal transplant took place in 1906. The first US eye bank opened almost 40 years later, in the year 1944. Eye banks have an illustrious history and have been the stewards of the gift of sight throughout the world for over six decades. Eye banks are unique because they recover, evaluate, and distribute donor corneal tissue for transplantation, research and education. In 2005 alone, 31,947 corneas were transplanted in the United States. Additionally, 13,542 corneas were provided for research and 4,541 corneas were distributed for training purposes.

The Eye Bank Association of America (EBAA) is a national association that represents 80 US eye banks and 13 international eye banks. Since 1961, the EBAA has been dedicated to the restoration of sight through the promotion of eye banking by promulgating medical standards, accrediting eye banks, and certifying eye bank technicians. The EBAA also helps to promote collegial relationships among the various eye banks in the US to assure an adequate supply of corneas for patients in the US. These relationships have introduced scheduled surgery for corneal transplants;

to date, there has been no need for a registry to list the availability of corneas.

The EBAA was the first national transplant organization to establish medical standards (1980) and ethical codes of conduct. All EBAA member eye banks voluntarily submit for EBAA inspection; following inspection, an EBAA Accreditation Board meets to review the observations and to determine whether or not to accredit the eye bank. Accreditation of eye banks is awarded for up to three (3) years. The Association works closely with eye banks to provide resources for them to achieve the maximum 3-year accreditation status. In conjunction with the American Academy of Ophthalmology (AAO), the EBAA urges all patients, surgeons and health care facilities to work solely with organizations that are EBAA accredited. As there are marked differences in the medical, technical and practical aspects of organ, eye and tissue donation, the three categories of anatomical gifts have evolved as distinct specialty areas. Organ, eye and tissue donation differ significantly in their medical standards, federal regulatory requirements, timeliness of donor access, number of potential donors, costs structures and philanthropic community support. Anatomically, the cornea is thought to be uniquely protected from infection, significantly reducing the potential for transmission of systemic infectious diseases. Corneas are avascular and are bathed in clear fluids, namely, aqueous humor posteriorly and tears anteriorly on the corneal surface. Infectious agents that travel within the vascular tree, must exit the blood stream, and invade and permeate the clear aqueous humor and tears to reach the cornea. Viral adherence to the cornea may be inhibited by the proteins in these clear fluids. If there is significant gross bacterial contamination, it is often readily evident on slit-lamp microscope inspection of the clear cornea. This differs from bone, skin, and other tissues, which by their physical nature cannot be as readily inspected. Medical literature often refers to the cornea as “privileged” because of the absence of blood vessels, that in other anatomical sites, transport antigens and pathogens from the donor to the recipient. The relatively low rejection rate and the relative absence of systemic disease transmission through transplanted corneas are known to be attributable to the “privileged” nature of the cornea. When corneal avascularity is combined with strict donor screening criteria, the opportunity for systemic infectious disease transmission has proven to be virtually nonexistent, although it can occur. Timeliness is another critical issue that distinguishes eye recovery from organs and tissues. Delicate corneal cells remain viable for only a short period of time following death. Unlike many tissues that can be stored for extended period of time, the cornea can only be

preserved for a matter of days. Eye banks must attempt to gather all necessary medical data from multiple sources, interview the next of kin, and receive blood test results in as short a time as possible following the death of a donor. The information below outlines the thorough process that eye banks undertake to recover donor corneal tissue and ensure that it is safe for corneal transplantation. At each step, attention to detail and quality is of paramount importance.

Eye Banking: The Process from Donor to Recipient

The Call

An eye bank receives a call from a hospital or an organ procurement organization or another “federally designated” third party, that an individual has died, and has met preliminary criteria for donation. The eye bank has a very short time within which to contact the next of kin, obtain consent and recover the tissue. This generally needs to happen within 12 hours from the time of death.

The Contact

The eye bank contacts the next of kin, as defined by the state law and the Uniform Anatomical Gift Act (UAGA), to obtain consent for the donation of the individual’s corneas.

The Consent

If a consent is given, the next of kin is asked to complete a medical-social history. The medical-social history provides the eye bank with information to make a donor eligibility determination.

The Donor Medical Review

After the consent is given, the eye bank obtains copies of relevant medical records for review from the hospital, a step in the process of creating a complete donor profile. Eye banks pay close attention to the cause of death, any medications that were administered to the individual and if there was any blood loss.

The Physicial Inspection

In the absence of any medical “rule outs,” an eye bank technician performs a physical inspection of the donor. This physical inspection contributes to the donor profile, and screens for physical signs of infectious disease or behavior that may have put them at risk, such as

intravenous drug use. The technician also draws a sample of blood from the donor to be tested for HIV I and II, hepatitis B & C, and syphilis.

The Recovery

The donor’s eyes are then prepared for the procedure to recover the cornea. The technician wears a sterile gown and gloves, and drapes the donor eye to establish a sterile field. While the technician makes certain that the sterile field is not contaminated, the cornea itself is not considered sterile.

The Storgae

After removing the cornea, the tissue is placed in a storage medium. This medium keeps the tissue viable and helps to reduce bacterial growth. The technician then transports the cornea to the eye bank’s laboratory for refrigeration.

The Evaluation

Specially trained eye bank technicians evaluate the donor cornea through microscopes to ensure that it meets the eye bank’s strict criteria for corneal transplantation.

The Eligibility Determination

The eye bank’s medical director or his/her designee reviews the records for the donor and makes a final eligibility determination.

The Release of Tissue

If the medical director or his/her designee authorizes release of the tissue, the cornea is then sealed and packed in a container in wet ice (to ensure it remains between 2-8 degrees and does not freeze).

The Transport

The cornea is labeled with a unique identification number to allow the eye bank to track the tissue from the donor to the recipient. It is then shipped to a surgeon or another eye bank for corneal transplant. Eye banks take their stewardship of the gift of sight very seriously. They train their staff to ensure that the recovered tissue is safe for corneal transplantation and is of the highest quality.

The EBAA holds eye banks to a high level of professionalism through the promulgation of medical standards, a stringent accreditation program, examination and certification for technicians, research grants, and continuing education seminars and scientific sessions.1

The demand for donor corneal tissue in the United States has increased dramatically over the last two decades. Cornea transplantation has become a major means of visual rehabilitation for several corneal disorders such as:

1.Pseudophakic bullous keratopathy.

2.Aphakic bullous keratopathy.

3.Advanced keratoconus.

4.Previous graft failure.

5.Significant corneal scarring, secondary to infection,

trauma, etc.

Currently, the number of corneal transplantations is under 40,000 per year, according to data from the EBAA. The demand of corneal tissue for transplantation is influenced by changes and the indications for PKP. These indications appear to change with the passing years. We have seen in the past literature, that the number of keratoplasties for pseudophakic and aphakic bullous keratopathies have changed according to the changes in the cataract surgery techniques.

The criteria for corneal tissue required for PKP as set by the FDA were finalized in May 2004. In addition to screening and testing for HIV and hepatitis, as was done under an earlier regulation, the new regulation requires screening for diseases such as syphilis, West Nile virus, severe acute respiratory syndrome (SARS), and the neurological condition Creutzfeldt-Jakob disease (CJD).

No lab tests are currently available to test for West Nile virus, SARS, and CJD. To identify a potential risk for these diseases, a tissue bank representative interviews the family of the deceased donor. Interviewers at Donor Alliance typically have social work or psychology backgrounds, says Mansfield, and they ask about 50 questions to gain extensive information about the donor’s medical and lifestyle history that may signal a risk, including sexual practices, injectable drug use, and travel history. Donors who lived in Britain, for example, at the height of the “mad cow” epidemic are excluded from donating because they are considered at risk for the human form of mad cow disease, a variant of CJD.

To further protect transplant recipients, the donor eligibility rule builds in flexibility for the FDA to require screening for new disease threats as they emerge and reliable tests become available. Donor tissue cannot be released for use until all screening and testing processes are completed and medical experts review and evaluate the results. An exception may be made in the event of an urgent medical need where no suitable tissue is available and the recipient is likely to become gravely ill or die without the tissue (does not usually apply to corneas). Any donor found to have infected tissue or found to be at risk for infection is considered ineligible, and, with rare exceptions,

all tissue from that donor is destroyed or used only for research or educational purposes. http://www.fda.gov/ fdac/features/2005/305_tissue

Overview of Supply of Donor

Corneal Tissue

EBAA’s membership is comprised of 92 US member eye banks, a participation rate of 99% of the eye banks in this country. Our member banks provide approximately 97% of all corneal tissue for transplantation. All eye banks are 501(c)(3) organizations whose sole mission is to procure and provide donated human eye tissue for sight restoring transplantation procedures. The EBAA takes pride in ensuring the highest standards of safety for our member eye banks to practice and has established strict Medical Standards that are reviewed and revised annually. To be accredited, EBAA members are subject to an inspection and certification program to demonstrate adherence to such standards and other requirements.

EBAA member banks provided 46,532 corneas for transplantation in 2001.2 A total of 83,075 were actually procured, with the difference deemed unsuitable for transplantation. These corneas did not meet strict eye bank standards, and based on exclusionary criteria, were not used for transplant, but were instead provided for research, education, or destroyed.

Corneas are a gift of human eye tissue made by the donor prior to death, or by the donor’s family following the donor’s death. As a gift from a human donor, a supply cannot be ordered or assured. Further, a supply cannot be maintained, because a cornea loses its viability within several days of procurement. To meet the need of approximately 46,000 corneas each year, it is necessary to procure approximately twice the amount of donor corneal tissue. The future availability of corneas for transplant procedures is uncertain, given the increasing use of LASIK and other surgical procedures which modify the cornea. Currently, individuals who have undergone these procedures are not considered suitable donors for corneal transplantation. In the past five years alone, there has been a sharp increase in LASIK procedures, doubling from 1997 to 450,000 in 1998. The number of procedures in a five year period totals 5,415,000. This is cumulative and increasing and could well adversely affect the supply of corneas for transplantation. The future demand for transplantable corneas and ocular research tissue is likely to increase. The National Eye Institute and Prevent Blindness America released a report in March of this year, concluding that more Americans than ever are facing the threat of blindness from

age-related eye disease. “Over one million Americans aged 40 and over are currently blind and an additional 2.4 million are visually impaired. These numbers are expected to double over the next 30 years as the Baby Boomer generation ages.”3

In order to ensure a sufficient supply of corneal tissue for transplantation, necessary for the restoration of sight, eye banks must collect and distribute corneal tissue within strict time parameters and in sufficient volume to meet the need.4 At the present time there has been an increasing interest among corneal surgeons in lamellar corneal surgery [See also Section 8, Deep Lamellar Endothelial Keratoplasty (DLEK), and Section 9, Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)], a gradual change in direction from full-thickness penetrating keratoplasty to partial thickness lamellar corneal surgery. Factors contributing to the increasing popularity of lamellar keratoplasty include the development and continued improvements in the microkeratome, the introduction of artificial anterior chambers (See also Chapter 12, Artificial Anterior Chambers), improved surgical instrumentation (See also Chapter 11, New/Useful Surgical Instruments in DSAEK), and simplified surgical techniques (See also Chapter 23, DSAEK Simplified Surgical Technique). Anterior lamellar keratoplasty (ALK) (Figure 19-1) for corneal stromal diseases and scars with a healthy recipient endothelium, and posterior lamellar keratoplasty (PLK) (Figure 19-2) such as deep lamellar endothelial keratoplasty (DLEK), Descemet’s stripping endothelial keratoplasty (DSEK), and Descemet’s stripping automated endothelial keratoplasty (DSAEK) are alternative surgical techniques to a fullthickness PKP for host endothelial cell failure.

Figure 19-1: Schematic representation of anterior lamellar keratoplasty.

Figure 19-2: An illustration of the donor corneal tissue in blue replacing the removed, host Descemet’s membrane and endothelium in DSAEK procedure.

This relatively popular technique - DSAEK, relies on the observation that many causes of corneal decompensation occur as a result of corneal endothelial dysfunction, and that replacing the endothelium without transplanting the entire cornea is sufficient to restore vision. These techniques offer a clear cornea without any significant surgically induced corneal astigmatism, no corneal wound and the absence of corneal sutures. Furthermore, since the donor endothelium can be inserted through a small incision in DLEK and DSAEK surgery, instead of an open-sky approach, the relative chance for an expulsive hemorrhage is less, and since there are no corneal sutures, the risk for infection in these procedures are expected to be much less as compared with a PKP procedure. Endothelial replacement research dates back to 1993 when Ko et al performed posterior lamellar transplantation experiments in rabbits (See also Chapter 14, History of Lamellar and Penetrating Keratoplsty). Posterior lamellar keratoplasty (PLK) was then attempted in cadaver eyes and primates through the mid-1990s, and Melles et al reported the first successful human PLK in 1999 (See also Chapter 14, History of Lamellar and Penetrating Keratoplsty). Since then, the technique has been further refined by Terry et al, who termed the procedure deep lamellar endothelial keratoplasty (DLEK). Theoretically, DLEK or DSAEK can be performed for nearly half of the 38,000 transplants performed each year in the United States, since nearly half of these procedures are due to vision loss from endothelial dysfunction. DLEK is a technically challenging procedure

[See also Section 8, Deep Lamellar Endothelial Keratoplasty (DLEK)] that relies on the surgeon’s ability to dissect into and through the corneal stroma, without perforating through the anterior surface of the cornea or into the anterior chamber. Both the corneal surface and the limbus are preserved in DLEK and DSAEK surgeries, and as such, it maintains the integrity of the globe. Keratoplasty has evolved over the last five years with the availability of elegant systems that offer artificial anterior chamber, microkeratomes that work in these artificial anterior chambers, and the ability for “sophisticated” preparation of the donor corneal tissue in vitro.

We have presented in the past our experience with the artificial anterior chamber and a microkeratome in ALK (Figure 19-1). In this procedure a microkeratome is used to prepare a donor surface lenticule, to replace a complete lamellar flap removed from the host by the same microkeratome. More recently, the advent of DSAEK procedure has made it a clear indication for most endothelial cell failures. The actual parameters required for the donor corneal tissue with this procedure have changed. In DSAEK, the preparation of corneal tissue

A

B

Figure 19-4: Schematic representation of the donor corneoscleral button within the Moria ALTK system.

Figure 19-5: A 350 µm LSK-microkeratome (Moria Inc., Antony, France) is assembled to perform a complete pass and remove the anterior 350 microns of donor tissue as a “free-cap.”

Figure 19-6: Schematic representation of the encased donor corneoscleral button within the Moria ALTK artificial anterior chamber with the LSK guide ring in place.

C

Figures 19-3A to C: The placement of a large corneoscleral donor button endothelial-side down within the Moria ALTK system and the rings are attached and tightened (Moria Inc., Antony, France).

Figure 19-7: Diagrammatic display of the donor corneal tissue without the free-cap, after a complete pass with the LSK microkeratome.

requires a large corneoscleral button ideally over 14 mm in diameter. This will enable the successful donor tissue fixation within the artificial anterior chamber (Figures 19-3 and 19-4) and subsequent harvesting of the donor

deep stromal-endothelial button using an automated microkeratome and an artificial anterior chamber (Figures 19-5 to 19-7). The donor cornea is then trephined from the endothelial side using a disposable Hanna trephine with

Figure 19-8: The microkeratome cut donor corneal button is flipped over on itself such that the endothelial side is facing up on the cutting block and trephination is carried out using a Hanna trephine to create a corneal lenticule of a pre-determined diameter (8.75 mm in this example).

Figure 19-9: The Hanna trephined lenticule.

Figure 19-10: Schematic representation of trephination of the donor corneoscleral button using a Hanna trephine with a diameter of 8.75 mm.

a diameter that the surgeon chooses (Figures 19-8 to 1910). The donor lenticule is then folded as a 60%/40% fold with a strip of Healon within the “taco” fold (Figures 1911A and B) and it is now ready for insertion into the recipient anterior chamber.

A

B

Figures 19-11A and B: The prepared donor lenticule is folded and ready for insertion into the recipient anterior chamber.

DLEK and DSEAK procedures have been changing the offered tissue trends in several eye banks in the US. An increasing number of eye banks in the United States now offer pre-cut corneal tissue with an automated microkeratome and an artificial anterior chamber (See also Chapter 30, Use of Eye Bank Pre-cut Donor Tissue in DSAEK). The most popular device for the donor corneal preparation has been the one made by Moria (Moria Inc., Antony, France) (See also Chapter 12, Artificial Anterior Chambers).

Donor corneal tissue that had previous LASIK surgery, is currently not offered by the eye banks as a donor cornea for transplantation. Since LASIK surgery has altered the cornea with regard to an intrastromal wound with altered biomechanics, it is not suitable for full-thickness PKP procedure. Since, only healthy donor corneal endothelium is required along with the deep corneal stroma for PLK procedures such as DLEK, DSAEK, it will be interesting to see whether in the future such corneas will be offered by

eye banks for PLK procedures. Superficial corneal trauma as well as superficial corneal scar are another contraindication for donor corneal tissue for PKP. Again, this may not necessarily be a contraindication in the future for tissue use in DLEK and DSAEK surgery and eye banks may change their policy regarding such donor corneal tissues with healthy endothelium and deep corneal stroma.

We have been using the 350 µm head with the LSK microkeratome (Moria Inc., Antony, France) in order to remove 320 to 380 µm of anterior cornea [See also Section 9, Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)]. The corneal donor button is then trephined endothelial side up with a disposable 8.75 mm trephine blade and the Hanna donor block (Moria Inc., Athony, France).

The reported results with the DSAEK procedure are very promising and there is a continued interest among corneal surgeons regarding the DSAEK procedure. Currently, many of the eye banks do provide pre-cut donor corneal tissue for those surgeons requesting pre-cut tissue for their DSAEK procedure. The appropriate donor tissue would be screened in the eye bank following necessary steps that are very similar to the current protocol in use. Use of pre-cut donor corneal tissue would significantly shorten the operative time. However, one has to keep in mind the tissue is cut by an eye bank technician and there is an additional charge by the eye bank for providing pre-cut donor corneal tissue

(Editorial Note: “Surgery by surgeons” is somewhat modified in this setting. Healthy donor corneal endothelium is an important part of this transplant surgery. Currently, a new CPT code has been established in the US that will pay a surgeon fee for cutting

the donor corneal tissue by the surgeon in the operating room at the time of DSAEK surgery). The procedure would then entail the incision and removal of the host Descemet’s membrane, followed by the folding of the prepared endothelial donor corneal disk and insertion into the recipient anterior chamber.

The use of the Femtosecond laser, has become popular both in the USA and internationally. This technology currently provides bladeless LASIK procedure. This technology has recently been used in the preparation of the donor corneal tissue for DSAEK surgery.

Continuing technique refinements and studies will determine whether the overall graft survival in DSAEK is comparable to that of a PKP. DSAEK is currently a new but established alternative to PKP which is the golden standard treatment for most visually debilitating corneal diseases. Ongoing studies and further experience with the DSAEK procedure will determent the variability of this technique and the serious consideration from eye bank strategy in the USA and internationally, can facilitate the specific tissue needs that this new technique poses.

References

1. News from the EBAA, The uniqueness of eye banking: Eye Banks ensure the safe supply of corneal tissue for transplantation, research, and education – August 31, 2006.

2. Eye Bank Association of America. Statistical Report, 2002.

3. US. Department of Health and Human Services, Press Release: “More Americans Facing Blindness Than Ever Before.” March 20, 2002.

4. Keeping Human Tissue Transplants Safe. www.fda.gov/fdac/ features/2005/305_tissue.html