Ophthalmologists work globally to combat cornea transplant tissue shortages

Despite many challenges, eye banks continue to grow worldwide, providing an invaluable contribution to the advances, safety and success of corneal surgery.

In Western countries, eye banks have a solid network of services, covering wide areas and efficiently meeting the growing demand for eye tissues. In other parts of the world, where the demand is even greater due to the high rate and multiple causes of corneal blindness, the population is still underserved. However, international associations are tirelessly working to reach these people and address their needs.

Recent data published by the Eye Bank Association of America, the European Eye Bank Association and Vision 2020 provide insights into the differing situations.

In the U.S., 85 domestic eye banks reported 110,600 donations in 2010. A total of 59,271 corneal grafts were supplied, and 42,642 corneal transplants were performed.

In Europe, approximately 20,000 corneal transplantation procedures are performed each year, and 35,000 corneas are procured.

In India, the country with the world’s largest corneal blind population, there is a need for about 100,000 corneas annually. But there are only about 17,000 eyes procured a year, of which only about 50% to 60% are utilized.

Successful eye bank development depends on the synergistic balance and interaction among laws, professional health services and community engagement. Increasing public awareness, promoting eye donation, implementing medical and quality standards, and organizing a solid network of trained professionals for the procurement, preservation and distribution of tissues are some of the key issues that eye banks worldwide need to address.

United States

A strong focus on research characterizes the mission of the Lions Eye Institute for Transplant and Research (LEITR) of Tampa, Fla.

“We were founded as an eye bank. Then we started supplying eye tissue for research to industries and academics. Recently, our advisory board decided to set up a large research center within the eye bank,” Jason Woody, president and CEO of the Lions Eye Institute, said.

LEITR is one of the largest eye banks and the only combined eye bank and ocular research center in the world, collecting approximately 7,000 human eyes per year. About 3,000 are qualified for corneal transplant, while the rest are used for research purposes. Researchers are offered facilities to live and work within the eye bank premises, using eye tissue that is 4 to 5 hours old from donor’s death.

“We offer a high volume of human eyes to work with and a very low death-to-preservation time as well as the most advanced technologies for research,” Woody said.

“We also offer a unique opportunity to do research on specific eye conditions. We receive the medical history of the donors and categorize the donor eyes by disease. Researchers can work on large samples of freshly collected human eyes with specific diseases like AMD, glaucoma or diabetic retinopathy, reducing the need for animal testing,” he said.

Medical devices, including new drug delivery systems, can also be tested in eye bank eyes.

“We hosted a joint project of a Swedish university and Emory University on a new drug delivery injection technique. Thanks to the significant access to donor eyes, they were able to carry out their research in 1 week rather than 6 months,” Woody said.

“While people are here, new donor eyes constantly arrive, and they are able to use them immediately,” he said.

Europe

The availability of donated corneas is high in Europe, although donation is not consistent among countries or even areas within the same country.

“While Italy, Spain, the U.K. and France have very high rates, northern countries are unable to meet the internal demand. Impractical legislations are often to blame,” Jesper Hjortdal, MD, PhD, vice president of the European Eye Bank Association, said.

The European standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of eye tissues were set in 2004 by the European Parliament. Within this framework, national regulations can vary to some extent.

“Corneas for transplantation are normally harvested within 24 hours from death by doctors or trained technicians. Together with a blood sample of the donor, they are transferred to the eye bank, where they are examined at the slit lamp and then incubated in organ culture medium at the temperature of 31°C. The blood sample is tested for transmissible diseases,” Hjortdal said.

Corneas are tested again, after a maximum of 5 weeks of storage, and qualified for transplantation if the endothelial cell count is more than 2,000 cells/mm². They are then moved to a deswelling medium containing dextran, which osmotically makes corneas thinner for easier surgery. Finally, the corneas are delivered to surgeons.

Most eye banks have facilities to provide pre-cut tissue for specific transplantation procedures, but some surgeons still prefer to cut the tissue on site.

“One of the great advantages of pre-cutting tissue is that now, with lamellar techniques, you can use one cornea to provide two grafts, one anterior and one posterior, and both grafts have been quality checked in the bank,” Hjortdal said.

There are 70 European eye banks, but only four have facilities for large distribution at the national or international level: Beverwijk, Netherlands; Bristol and Manchester, U.K.; and Venice, Italy.

Integrated model

The Veneto Eye Bank Foundation in Venice is the most active eye bank in Europe in terms of volume.

“We have developed a small integrated model where, in addition to the core activity of eye banking, procurement and distribution, we are engaged in professional and community education, research on regenerative medicine, and diagnosis and counseling for complex ocular surface disease,” Diego Ponzin, MD, medical director of the eye bank, said.

The eye bank relies on more than 2,000 donations a year from the northeast regions of Italy. It distributes ocular tissue to transplant centers throughout Italy, covering 40% of the internal requests, and to 15 countries in Europe and 10 outside Europe. It has unique capabilities for providing high-quality pre-cut tissues for all the latest lamellar techniques, including endothelial transplantation. It also procures and distributes human amniotic membrane for ocular surface reconstruction and was first in the world to produce and distribute grafts of corneal stem cells reconstructed in vitro for the treatment of ocular pathologies that cannot be treated by corneal transplantation alone.

“We are also working at gene therapy. In 2006, we reported the first-ever successful case of gene therapy for a rare genetic skin disorder in one patient transplanted with a skin graft made of genetically corrected stem cells,” Ponzin said.

Optimization of preservation and preparation techniques for long-term transplanted graft survival is another area of research within the eye bank.

Asia

Unlike in the U.S. and Europe, the number of patients in Asia who need a corneal transplantation greatly exceeds the number of corneal donations, according to Donald T.H. Tan, MBBS, FRCSG, FRCSE, FRCOphth, president of the Association of Eye Banks of Asia (AEBA) and OSN APAO Edition Board Member.

“There is a lack of donor tissue across the continent, with waiting lists numbering up to thousands. Thailand has a major eye bank, but 2,000 patients are waiting for corneal transplant. Myanmar also has an eye bank organized for tissue procurement, but a waiting list of 3,000. Korea, Malaysia, Indonesia and Vietnam have eye banks, but are unable to procure more than 50 corneas a year,” he said.

Reaching out to eye banks and finding strategies for improvement are part of the mission of AEBA, but several issues need to be addressed.

Many areas in Asia have unfavorable or confusing legal frameworks for donation and lack funding and infrastructure for health care.

“Eye banking is not a priority for legislators and health authorities in countries that are struggling to provide basic medical care,” Tan said.

In addition, the number and availability of specialized corneal surgeons and technicians are limited by lack of educational and training opportunities.

There are also few public initiatives regarding organ donation in these countries, which keeps awareness and acceptance of organ donation low.

“There are also some perceived religious, cultural and social impediments in some parts of the continent,” Tan said. “In Singapore, we realized that religious concerns were a core issue we had to deal with, and over 10 years ago we approached the main religious organizations. We have Hindu, Buddhist, Muslim and Christian religious groups, and it turned up that although the population thought there were religious blocks, all their leaders expressed in favor of organ donation.”

This finding and many public awareness initiatives have made Singapore one of the three countries where eye donation is high. The other countries are Sri Lanka, where the majority of the population follows a form of Buddhism that is proactive toward organ donation, and the Philippines, which has legislation on this matter.

“These three countries have very modern eye banks, with the best quality standards. AEBA has selected them as models and is helping representatives of other eye banks in Asia to go there and learn how to develop their own program,” Tan said.

Latin America

Eye banking in Latin America suffers from a lack of consistency, Mark J. Mannis, MD, FACS, immediate past president of the Pan American Association of Eye Banks (APABO), said.

“One of the largest and most active eye banks worldwide is based in Sorocaba, Brazil. More than 300 corneas a month are processed there. Colombia also has an efficient network of small, very functional eye banks. The rest of the subcontinent, including Central and South America and the Caribbean, has very poorly organized eye banks, far behind the U.S. in terms of functionality,” he said.

With corneal blindness being one of the most common causes of vision loss in the area, eye banks are not able to cover the need for transplantation, and donor corneas are mainly imported from the U.S.

Fostering eye banking programs in Latin America is a major goal of the APABO.

“We have educational programs for instructing doctors and technicians in eye banking procedures and quality standards,” Mannis said.

But there are challenges that go “beyond the walls” of internal eye bank practices, he said.

“A first major challenge is educating the public, which is mostly unaware of the need for donation in Latin America. Second is to enlist government support for eye banking. Third is to make physicians and administrators understand the importance of regionalizing eye banking. Having a myriad of small eye banks associated with one specific hospital or center is a practice that in the long run never works,” Mannis said.

Only once these challenges are met will Latin America be able to discontinue its dependence on the U.S. for tissue transplantation, he said.

Eye banks and surgery

With the development of new corneal transplantation techniques, eye banks have acquired an even more central role, Mannis said.

“With the increasing need for pre-cut tissue, it has become clear that eye banks are active partners in surgery,” he said.

Endothelial keratoplasty has rapidly gained popularity in recent years. In the U.S., the number of procedures has grown from 2,500 in 2005 to 22,000 in 2010.

“It’s almost half the total number of corneal transplantations,” Ponzin said. “In Italy, about 6,000 keratoplasty procedures are done each year, and now at least one-third are endothelial.”

“It’s a huge trend and an important innovation because lamellar techniques are less invasive, have less morbidity and lower costs for the health care systems,” Hjortdal said.

Anterior lamellar techniques have responded well to the needs of Asia, where corneal scarring from infectious diseases, trauma, and diseases affecting the front layers of the eye, such as trachoma, vitamin A deficiency and childhood blindness, are widespread.

“[Deep anterior lamellar keratoplasty] allows us to use corneas with lower endothelial cell density than PK. We have increased utilization by at least 15% in Singapore. The newly initiated National Eye Bank of Sri Lanka, an AEBA-affiliated model eye bank which has now raised eye banking standards in Sri Lanka to international levels, has a utilization of 93%, which is huge,” Tan said.

In Latin America, however, the most widely used technique is still PK.

“Hospitals don’t have the facilities to cut lamellar grafts, and most eye banks don’t provide pre-cut tissue,” Mannis said. “Without a solid network of functional eye banks, corneal surgery cannot progress.” – by Michela Cimberle

Which storage method has more advantages?

Organ culture allows time for thorough evaluation

Organ culture is a medium-term storage method to preserve donor corneas in an incubator at the temperature of 30°C to 37°C in a tissue culture medium, supplemented with fetal or newborn calf serum, antibiotics and antimycotics. It is currently the method of choice in Europe for a number of reasons.

First, compared with hypothermic storage, the allowed storage period is longer, up to 4 weeks. This time interval before transplantation is precious. It enables us to perform microbiological testing for safety, tissue typing and matching, to fix reversible post-mortem damage and to schedule surgery by selecting the most suitable corneas for each procedure. It permits greater flexibility in the use of donor tissue and prevents waste. It also allows a more thorough evaluation of the endothelium over the entire surface and the possibility to do vital staining before and after storage to help recognize dead or necrotic cells. In this way, corneal tissue with a defined endothelial quality can be delivered.

Organ culture is considered a stress test. There is a difference in cell loss during storage of individual corneas that reflects differences in vitality. Tissue with irreversibly affected vitality reveals itself by significant endothelial cell loss and necrosis of cells.

Donor tissue is usually contaminated. The antibiotics and antimycotics used in the medium are more effective if the contamination microbes are metabolically active at 30°C to 37°C. If the tissue is contaminated, it will become obvious more rapidly in organ culture because the micro-organisms grow. So the risk of transplanting contaminated tissue is reduced.

The procedure, to allow all this, is obviously more complicated and has higher costs compared with hypothermic storage. This, however, is compensated by the many advantages.

Ilse Claerhout, MD, is senior scientist of the research staff at Tissue Bank Gent, Belgium. Disclosure: Claerhout has no relevant financial disclosures.

Hypothermic storage more simple

Hypothermic intermediate-term storage allows preservation of donor corneas for up to 2 weeks, utilizing tissue storage media at 4°C. It is the most common method in the United States, where there is a relative abundance of tissue. The most commonly used storage medium is Optisol GS (Bausch + Lomb), a chondroitin sulfate and dextran compound that, at hypothermic temperatures, minimizes the thickening and opacification of tissue and protects the epithelium. Bacterial growth and tissue decomposition are minimal at 4°C. Antibiotics placed in the storage medium provide coverage against gram-positive and gram-negative organisms that might potentially develop after the donor cornea is warmed to room temperature intraoperatively and to 34°C postoperatively in the host.

The advantages of hypothermic storage are simplicity of technique, minimal equipment requirements (a 4°C blood bank type refrigerator) and minimal handling. The training of eye bank personnel is considerably less sophisticated compared with organ culture techniques. Potential damage to the tissue, should the temperature fluctuate above the intended 4°C mark, is minimal, and tissue is transferable by commercial transportation in Styrofoam containers with wet ice. Corneas that are not used can be returned and redistributed as long as they are maintained within the appropriate temperature range.

Because of the relative simplicity of hypothermic storage equipment, corneas can be recovered in multiple locations and processed at the eye bank without excessive investment on infrastructure. Hypothermic medium is more easily transported to procurement sites and facilitates getting more donor corneas from remote areas. Utilizing the U.S. medical infrastructure for evaluation of medical records, physical examination of the donor and serology, corneas can be recovered from nearly any consenting donor in the United States and placed in the Eye Bank Association of America distribution system to be delivered to any location in the world.

Compared with hypothermic storage, organ culture is costly, laborious and time consuming. In today’s world, cost may be the most important distinction.

Woodford Van Meter, MD, is treasurer of the Eye Bank Association of America. Disclosure: Van Meter has no relevant financial disclosures.

Ophthalmologists commit to donating eye tissue

Adding to the nearly 5,000 attendees already registered as donors, SightLife signed up an additional 400 eye, organ and tissue donors during the “Are You a Donor?” campaign at the joint meeting of the American Academy of Ophthalmology and Asia-Pacific Academy of Ophthalmology.

“Only 42% of adults in America are registered as donors,” Monty Montoya told Ocular Surgery News. “Physicians and other health care professionals can help improve that rate by demonstrating their commitment to donation.”

SightLife, founded in 1969, is the only nonprofit global health organization that is focused solely on eliminating corneal blindness around the world, according to its website. The “Are You a Donor?” project was developed to increase donor commitment by enlisting the help of ophthalmologists and ophthalmic professionals to encourage their peers and community to register as donors.

Further information is available at AreYouaDonor.org.