Ординатура / Офтальмология / Английские материалы / Eye Banking_Bredehorn-Mayr, Duncker, Armitage_2009

Follow up (months)

Fig. 9. Success rate of grafting: 5-year graft survival.

UK. The EEBA has now grown to include (in 2006) 79 member eye banks. The number of corneas retrieved and processed in 2005 was almost 35,000. The majority of corneas passed through organ culture but a substantial number is still used after cold storage.

Another purpose of the EEBA was to set standards for eye banking. At the meetings the rules, recommendations etc. were discussed. The viewpoints of the EEBA were gradually formulated, and today an annual directory is published [25] (fig. 10).

European Union Regulations

The entire area of organ donation, retrieval and handling of organs and tissues has become an issue of greatest interest. One driving force was the fear of transferring diseases to the recipients.

Legislations regulating transplantation of corneal tissue have varied considerably between national states. In some countries, the cornea has been considered a piece of tissue, in other countries it has been looked upon as an organ. The Directive 2004/23/ EC of the European Parliament and of the Council of March 31, 2004, is within the near future going to set the standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells – including corneal tissue.

The main objective of the directive is to ensure the quality and safety of tissue transplantations, particularly in order to prevent transmission of diseases. The directive is followed by two appendices specifically defining (1) certain technical requirements

for the donation, procurement and testing of human tissues and cells (Commission Directive 2006/17/EC) and (2) technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells, now published as Commission Directive 2006/86/EC. The net effect of these directives which will later be implemented in the legislation of the national states will ensure a certain minimal standard also of corneal donor tissue within Europe. On the other hand, the directives will impose a significant administrative burden on each of the many European corneal banks.

Future Developments in Eye Banking

In most eye banks, the organ culture technique has not been modified considerably throughout the last 20 years. Fetal calf serum is used in most banks to enrich the tissue-preserving properties of the culture medium. Due to fear of prion transmission from cattle to human recipients of corneal tissue potentially leading to variant Creutzfeldt-Jakob disease, there has been significant interest in developing a fully synthetic and defined culture medium for corneal organ culture [26–28]. Such media have now been developed, and prospective experiments are ongoing to optimize medium composition.

Corneal rejection directed towards the endothelial cells of the grafted tissue remains one of the main causes of graft failure. Histocompatibility between host and recipient with respect to class II [29, 30] (fig. 11) and/or class I [31] improves graft prognosis in high-risk cases and maybe also in normal-risk cases after keratoplasty [32]. The waiting time to find a good match between donor and recipient depends on

the number of donor corneas available and tested and on the frequency of the recipient tissue type (and subtypes) in the donor population. With a small supply of donor tissue, it may take years to find an optimal match. Further international collaboration between eye banks may in the future increase the pool of donors and shorten the waiting time.

After establishing methods for the isolation and in vitro cultivation of human corneal endothelial cells, isolated transplantation of endothelial cells may be an alternative therapeutic option [33]. With the techniques of modern molecular biology, it may be assumed that cultured endothelial cells with low expression of histocompatibility antigens can be manufactured – or even that the recipient’s own endothelial cells can be made to proliferate in vitro and be autotransplanted back to the patient. This latter approach seems to be possible today for epithelial cells [34].

Development of a purely synthetic cornea would be the ultimate way to overcome the relative lack of suitable donor tissue and the ever more important burden of administrative work related to transplantation of human tissue. Today, promising results from a recent study suggest that lamellar corneal grafts may be produced synthetically [35].

Development of a purely synthetic cornea is also the target for international research programmes (Centres nationaux de la recherche scientifique).

Graft Optics

With an established surgical and banking technique, another problem becomes evident. Grafted corneas are only occasionally spherical. Some degree of astigmatism

is the rule. Average values in clinical series are around 2–4 dpt. In addition higherorder optical aberrations often compromise the visual result. This optical problem is approached from two sides. Laser reshapening of the surface after suture removal would seem to be a manageable solution. Results may be good but another timeconsuming surgical procedure rarely excites the patient. Therefore attempts are made to avoid astigmatism, e.g. by laser excision of the graft and recipient cornea (non-mechanical technique), a refined suture technique or mechanical stabilization by metal or plastic inlays, or increasing the tissue stiffness by molecular crosslinking.

Development of new lamellar surgical techniques for changing either the anterior or posterior part of the cornea is promising. Anterior lamellar grafting is used in keratoconus and other stromal dystrophies with the advantage of avoiding transplantation of endothelial cells [36]. Posterior lamellar grafting can be used in Fuchs’ dystrophy or secondary bullous keratopathy. In the more recent techniques, the socalled Descemet’s stripping endothelial keratoplasty, removal of the dysfunctioning endothelium and underlying Descemet’s membrane, is performed through a peripheral 5-mm corneal incision [37]. The advantage is faster visual recovery, less astigmatism and a more stable eye compared with the traditional penetrating keratoplasty procedure.

Niels Ehlers

Department of Ophthalmology, Århus University Hospital Nørrebrogade 44

DK–8000 Århus C (Denmark)

Tel. +45 89 49 32 22, Fax +45 86 12 16 53, E-Mail neh@tdcadsl.dk

•contribute to the development and maintenance of standards;

•establish and maintain an agreed set of EEBA standards;

•promote data collection on graft outcome in order to validate techniques;

•facilitate the interchange of information between banks;

•provide opportunities for the discussion of all aspects of practice including eye donor selection and procurement;

•encourage relevant research and development;

•provide informed comment to external agencies;

•foster education and training;

•maintain national and international links with corneal transplant communities and relevant bodies;

•make knowledge in the field of eye banking available to any person for the general good of society.

Background

The first meeting of the EEBA took place in Århus, Denmark, in 1989. The handful of people present, invited by Prof. Niels Ehlers, could not have known how the organization would develop, only that there was much to learn and share about eye banking. This open-minded approach is surely one of the reasons why the EEBA is today a successful organization.

Whilst relative informality has always been a key characteristic of the EEBA, recent developments in the regulation of tissue banking in EU member states [1–3], have meant that the Association has needed to revise its objectives, rules and finances. Therefore, in September 2002, the EEBA Committee met for the first time between annual meetings to be briefed on and discuss new developments prior to the regular annual meeting.

At that time it was decided that a part-time secretariat would be established and hosted at the Veneto Eye Bank Foundation in Venice (Italy). In addition, the elected members of the EEBA Committee were clearly defined as the President, Vice-President, Secretary, Treasurer, the Technical Representative and 7 Region Officers, all with voting rights and terms of office of 3 years. Additionally, the Directory Supervisor, the Chair of the Medical Special Interest Group (SIG), the Website Manager, the organizer of the next annual meeting and the organizer of the previous year’s annual meeting were confirmed as ex officio members of the Committee.

Standards

The EEBA maintains a set of recommendations (‘Agreements on minimum standards’) [4] relating to the medical assessment of donors and contra-indications to

Table 1. Number of responding eye banks (biennial data shown)

transplantation of ocular tissues. These standards are subjected to a formal annual review by the Medical SIG but may be reviewed more frequently should the need arise. The review takes into account current professional guidance [5] and clinical practice, as well as relevant national and international regulations. Recommendations from the Medical SIG for amendments and/or additions in the light of changing standards and practices are put to the EEBA Committee for approval.

In addition, the EEBA has established a series of ‘Technical guidelines for ocular tissues’ [6] which define the minimally accepted standards of quality and safety for the procurement, retrieval, processing, storage and evaluation of corneal and scleral tissue for transplantation. These standards are subject to periodic review by the Technical SIG, and any proposals for changes must be submitted to the EEBA Committee for approval.

Changes to the EEBA standards approved by the Committee must be agreed by members at a business meeting of the Association. At least 21 members must be present and two thirds of those voting must be in favour before any change is fully implemented.

Directory

Details concerning technical aspects of European eye banks, along with a yearly overview of the activities of those banks, have been collected and presented since 1991 in the form of an annual directory, published in time for the annual meeting [7–9]. Unfortunately, not all banks submit annual data, and therefore some analyses do not include all the statistics from the total number of banks present in Europe (table 1).

Table 2 shows the differently sized banks, arbitrarily divided according to their activity, expressed as number of corneas issued per year.

The decrease in the percentage of corneas issued for transplantation, over the period 1991–2007, can be attributed to the more stringent quality and safety standards and regulations with regard to donor screening, serological and microbiological testing and corneal evaluation criteria (e.g. minimal endothelial cell density accepted; table 3).

Table 2. Number of differently sized banks

Table 3. Percentage of corneas discarded/unsuitable for transplantation

Organ culture remains the preferred routine storage method in Europe. In 2007, organ culture was used by 46 banks (70%), hypothermic storage by 13 banks (20%) and 7 banks used both methods together (10%).

The minimum criteria for donor selection are those laid down by the EEBA, although many member eye banks apply additional donor criteria and contra-indications (table 4).

The Association is committed to encouraging banks to produce standard operating procedures and to put into action a quality management system, based on the principles of good medical practice and in accordance with the requirements laid down by national authorities responsible for the accreditation, designation, authorization and licensing of tissue establishments in compliance with the EU directive (table 5).

Membership

Individuals who wish to become EEBA members will be expected to share the aims of the Association and abide by the EEBA standards. Membership is on an individual

Table 4. Criteria for acceptance and contra-indications additional to those of the EEBA

Table 5. Quality management

Figures in parentheses indicate those in preparation. EBAA = Eye Bank Association of America.

basis (ordinary member), and each member is required to pay an annual subscription fee in order to receive the following benefits:

•a registration fee discount for the EEBA annual meeting;

•inclusion in the EEBA directory (provided that data are delivered in time);

•a personal copy of the EEBA newsletter;

•access to training opportunities;

•right of entry to the members-only section of the website.