Eye experts in Southampton have discovered people who have received liver transplants have an increased risk of developing age-related macular degeneration (AMD), which is a leading cause of blindness in the elderly.
In a pioneering study, a team led by Professor Andrew Lotery at Southampton General Hospital found that almost two-thirds (65%) of patients had some form of AMD and have suggested the introduction of regular optician monitoring for all liver transplant recipients.
During the three-year project, they studied 223 Western European patients 55 years and over who had undergone liver transplants at least five years ago to find out more about the relationship between the complex eye condition and liver transplantation.
Scientists had already revealed that a mutation which causes a gene in the liver – called complement factor H (CFH) – to produce abnormal proteins is more common in AMD sufferers, possibly causing more inflammation in the eye.
The researchers wanted to find out if receiving a new liver without the fault had any effect on the development of AMD and inflammation in the eye to determine if treatment for the condition given systemically, for example intravenously, could be more effective than directly into the eye.
They examined for mutations in the CFH gene in recipients’ blood and in donor tissue, and found AMD was associated with the CFH gene mutation in the recipients’ original liver – receiving a liver with or without it had no effect on the development of the disease.
“This study has provided us with some invaluable insights into this complex eye disease and the intriguing science behind CFH,” explained Prof Lotery, a consultant ophthalmologist at Southampton General and professor of ophthalmology at the University of Southampton.
“As a result of this project, in which we were primarily looking at whether or not fault-free genes could affect development of AMD, we have discovered liver transplant patients have a high incidence of AMD and that was unexpected.
“However, with this knowledge, we now know much more emphasis should be placed on the eye health of liver transplant patients and that should involve regular and ongoing optician monitoring and prompt referral to ophthalmologists if AMD is detected.”
As levels of inflammation in the eyes caused by the CFH gene remained unchanged in patients with AMD after liver transplant, Prof Lotery said the findings imply CFH protein produced in the eye and not in the liver is responsible for the development of AMD mean therapies directed into the eye are more likely to be successful.
“Not only do our findings mean we now know much more attention should be paid to the eye health of liver transplant patients, the fact we know AMD is related to a recipient rather than the donor liver they receive implies systemic replacement of a mutated complement gene is not effective for AMD,” he said.
“At present, very large sums of money are being spent on clinical trials of intravenous treatments to try to treat complement gene mutations linked to AMD, yet our evidence suggests these may prove futile and that efforts need to be focused on direct treatments administered through the eye.”
Dr Sam Khandhadia, a research fellow in Prof Lotery’s vision group who conducted the research as part of his PhD, added: “This project helps us to understand a little more about how AMD develops and suggests that treatment in the eye aimed at the inflammation-related proteins will be more effective than systemic treatments given intravenously.”
The research, published online in American journal Ophthalmology, was funded by TFC Frost Charitable Trust, Novartis UK, the Wellcome Trust and the Gift of Sight appeal and carried out in partnership with liver transplant units at Southampton General, Birmingham, Cambridge and Kings College London, and Professor Paul Morgan’s complement research group at the University of Cardiff.
Posted on Monday 22 April 2013