Cornea Transplant Failure | Action Medical Research | Children's Charity | Children's Charity

Blindness: Why do so many operations to transplant corneas eventually fail?

First published on 22 October 2008

Updated on 26 July 2012

What did the project achieve?

The main aim of this research was to find out why operations to transplant the cornea – the transparent window at the front of the eye – are so likely to fail in people who’ve been blinded by herpes infections (the virus that causes cold sores). If successful, these operations can restore people’s sight. If they fail, vision problems return.

“Our findings suggest that the most likely reason for the failure of corneal grafts in people with herpes infections is an exagerrated immune response to the virus,” explains Professor John Forrester. “The herpes virus can lie dormant in the body. Although there does seem to be some re-awakening of the virus after transplants, re-infection of the cornea by the virus does not seem to be the primary reason for the failure of transplants. The immune response seems to be more important.”

So, what next? “We believe that people with herpes infections who undergo corneal transplants are not given enough treatment to suppress their immune system. Developing better immune treatments, and combining them with anti-viral treatment, might improve the success rate of corneal transplants so more people can keep their sight. Our research into this possibility continues.”

The project leader, Professor John V Forrester, is now Emeritus Professor of Ophthalmology and Head of the Ocular Immunology Laboratory at the University of Aberdeen.

Action Medical Research is grateful to the The Hugh Fraser Foundation, The Souter Charitable Trust and The Stafford Trust for their support of this project.

This research was completed on 30 September 2011

Nearly one third of worldwide blindness is caused by diseases of the cornea – the transparent ‘window’ at the front of the eye.1 A corneal transplant can restore sight, but many transplants fail within 5 years, meaning people lose their vision for a second time.2,3 Researchers are investigating why infection with the herpes virus dramatically increases the chances that a transplant will fail. Ultimately, they hope to find ways to improve the success rate of transplants and save people’s sight.

What's the problem and who does it affect?

Devastating sight loss

Nearly one third of worldwide blindness is caused by diseases of the cornea – the clear tissue at the front of the eye.1 The main way to improve vision is a corneal transplant, more commonly called a corneal graft.

Corneal grafts are by far the commonest type of solid organ transplant in the world.2 Over 2,000 corneal grafts are performed each year in the UK alone.3 Sadly, many corneal grafts fail within 5 years.4,5 Indeed, the failure rate is higher than for other types of transplants, such as kidney transplants.4,5 It can be totally devastating for a person to go through surgery, and experience the joy of regaining their sight, only to lose their vision for a second time.

Infection with the herpes virus can cause the initial reduction of vision, which prompted the need for surgery in the first place, and then increase the chances that surgery will fail. Herpes is in fact the commonest infectious cause of corneal blindness in the developed world and is second only to trachoma in developing countries.

No-one knows why herpes makes corneal grafts more likely to fail, and this badly hinders attempts to improve the success rate of surgery and protect people’s sight.

What is the project trying to achieve?

The role of herpes infections

The researchers are investigating why herpes infections of the eye make it more likely that corneal grafts will fail.

Herpes infections are common. For many people, they cause only cold sores. Once someone has been infected, the virus can ‘hide’ in the body, lying dormant within nerve cells. Later, the virus can ‘re-awaken’ – often at times of stress or when the immune system is weakened. This means symptoms tend to come and go.

Herpes can cause vision loss if the nerve supplying the eye becomes infected. Each time the virus is reactivated, it can travel along the nerves behind the eye and infect the cornea, causing a problem known as keratitis (inflammation of the cornea), which destroys the cornea’s clarity so the patient can’t see through it. Herpes can also stir up immune cells in the eye, causing inflammation, even when the virus is lying dormant.

It’s possible that corneal grafts might fail because of reactivation of the herpes virus, or because the immune system becomes stimulated to reject the transplanted tissue. The researchers aim to determine which of these two possible causes of failure is the dominant one, using in-depth laboratory studies.

What are the researchers' credentials?

Project LeaderProfessor J V Forrester FRCS FRSE FMedSci
Project team
  • Dr Lucia Kuffová, MD PhD CSc
  • Mrs Marie Robertson
  • Mrs. Rosie Dawson
  • Mrs Elizabeth Muckersie
LocationDepartment of Ophthalmology, Institute of Medical Sciences, University of Aberdeen.
DurationThree years
Grant awarded22 July 2008
Start date1 October 2008
End date30 September 2011
Grant amount£153,533.00
Grant codeSP4328

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The project leader, Professor John V Forrester, is head of the Department of Ophthalmology at the University of Aberdeen. He is an acknowledged expert in experimental corneal transplantation and the immunology of the eye, with an outstanding track record as a clinician-scientist. Professor Forrester has published extensively in peer-reviewed journals.

Dr Kuffová is a trained immunologist, a clinical ophthalmologist and an expert in experimental corneal graft surgery. Mrs. Marie Robertson, Mrs. Rosie Dawson and Mrs. Elizabeth Muckersie are trained technicians who are involved in laboratory and animal work.

The project team is uniquely placed to investigate why corneal grafts are so likely to fail in people who have herpes infections and to look for ways to prevent graft failure. They have more than ten years’ experience in the use of an experimental model of corneal graft. More recently, with help from colleagues in Pittsburgh, they have established a laboratory model of herpes keratitis. They are the only group in the world who are using these models to study why herpes keratitis makes corneal grafts so likely to fail.

Who stands to benefit from this research and how?

Ultimate hopes of protecting vision

Herpes infections of the eye affect people of all ages, including the young. They cause recurrent pain, sensitivity to light, redness and irritation of the eye, blurred vision, watery eyes and progressive loss of vision. Corneal grafts can change people’s lives, by giving them back their sight, but all too many people go on to lose their sight again because their transplant eventually fails.

The researchers hope to reveal why corneal grafts are so likely to fail in people who’ve been blinded by herpes infections. This information is vital to the longer term goal of finding ways to boost the success rate of surgery and protect people’s sight.

If virus reactivation is the cause of graft failure, possible future treatments include vaccination. If immune rejection is more dominant, then researchers would need to look for safe ways to inhibit the immune response.

This research may also benefit people who have a corneal transplant for other reasons. Furthermore, as virus infection is also thought to compromise other types of transplants – of the heart and kidney, for example – information from this study may prove important to transplant success generally as well.

References

  1. Resnikoff S, Pascolini D, Etya'ale D, Kocur I, Pararajasegaram R, Pokharel GP, and Mariotti SP. Global data on visual impairment in the year 2002. Bulletin of the World Health Organization 2004;82:844-851.
  2. Brady SE, Rapuano CJ, Arentsen JJ, Cohen EJ, and Laibson PR. Clinical indications for and procedures associated with penetrating keratoplasty, 1983-1988. American journal of ophthalmology 1989;108:118-122.
  3. Bradley BA, Vail A, Gore SM, Rogers CA, Armitage WJ, Nicholls SM, and Easty DL. Penetrating keratoplasty in the United Kingdom: an interim analysis of the corneal transplant follow-up study. Clinical transplants 1993;293-315. (Unpublished data from the UK Transplant Service, Bristol, indicates that the number of transplants per year has probably risen since this publication.)
  4. Williams KA, Muehlberg SM, Lewis RF, Coster DJ. How successful is corneal transplantation? A report from the Australian Corneal Graft Register. Eye 1995; 9 (Pt 2) 219-227.
  5. Williams KA, Muehlberg SM, Lewis RF, Coster DJ. Long-term outcome in corneal allotransplantation. The Australian Corneal Graft Registry. Transplant Proc 1997;29:983.
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