Systemic immunosuppression may improve long-term graft survival in corneal transplants at high risk of rejection

A recent study from one of the five clinical sites for VISICORT, Bristol Eye Hospital, reports that systemic immunosuppression appears to improve long-term graft survival in corneal transplants at high risk of rejection.1

Paper authors Stuart Cook, Sing-Pey, Derek Tole pose with Shaun the Sheep

Paper authors Stuart Cook, Sing-Pey Chow, Derek Tole pose with Shaun the Sheep

Lead author of the study, Dr Sing-Pey Chow, reports: Immunological graft rejection remains the leading cause of graft failure in corneal transplantation. Systemic immunosuppression with medications such as tacrolimus and mycophenolate mofetil has been successfully used in renal and liver transplantation to improve graft survival. They are also used in corneal transplants at high rejection risk to prevent graft rejection, with the aim of improving graft survival.

This retrospective study reported graft and visual outcomes from 35 full-thickness corneal transplants at high risk of rejection in 29 patients receiving systemic immunosuppression, mainly with tacrolimus or mycophenolate mofetil as monotherapy. With the longest follow-up duration reported to date in high-risk keratoplasty recipients on systemic immunosuppression, 5-year graft survival in this cohort was 73.5%. Rejection episodes occurred in 14 grafts (40%), and episodes were reversible in 10 (71%) grafts. Average time to first rejection episode was 9.9 months, ranging from 1.2 to 15.2 months.

Severe systemic side effects occurred in 3 patients (10%), necessitating cessation of their systemic immunosuppression. This highlights the importance of diligently monitoring patients while they remain on these medications, as well as working closely with physician colleagues to optimise patient outcomes.

Along with co-authors Stuart Cook and Derek Tole, Dr Chow states: Over the next few years, VISICORT will generate a better understanding of adverse immune reactions to tissue transplants as biological samples from over 700 corneal transplant recipients in Europe and the UK is systematically profiled. This will in turn lead to new developments in surveillance, prevention and management of corneal transplantation, particularly for those at high risk of rejection.

This study was presented at World Cornea Congress 2015 in San Diego.

 

1 Chow S-P, Cook SD, Tole DM. Long-Term Outcomes of High-Risk Keratoplasty in Patients Receiving Systemic Immunosuppression. Cornea 2015, forthcoming.

New data from UK Transplant Registry shows similar 2-year rejection rates for full thickness and endothelial corneal transplants in first-time recipients

New data from UK Transplant Registry shows similar 2-year rejection rates for full thickness and endothelial corneal transplants in first-time recipients

Corneal transplantation involves the replacement of damaged cornea with donor tissue. For some of the commonest forms of corneal disease, there are currently two primary approaches to transplantation: Full-thickness, or penetrating keratoplasty (PK), which involves the replacement of the entire cornea, and endothelial keratoplasty (EK), which involves the selective replacement of the diseased layer of the cornea, leaving healthy areas intact. Over the past 15 years, EK has emerged as the preferred form of transplantation in cases of visual loss due to endothelial dysfunction. EK offers a number of advantages, by comparison with PK, including possible lower incidence of transplant rejection.

However, the theoretical advantages of EK have not always been reflected in the clinical data. To date, published studies have reported widely variable rates of rejection and subsequent graft failure following EK.

Newly published data from the UK Transplant Registry has provided further evidence that EK does not result in a lower incidence of transplant rejection and graft failure. The authors of ‘Transplant Rejection Following Endothelial Keratoplasty and Penetrating Keratoplasty in the United Kingdom: Incidence and survival’ report the results of 3,486 corneal transplants carried out in the UK for two specific corneal diseases and conclude that ‘there is no significant difference in rejection-free survival between EK and PK.’ They also report that the presence of inflammation can be an important risk factor for rejection suggesting that attention to its control before and following surgery is important. This finding highlights the importance of VISICORT’s work to investigate the markers of transplant rejection and to develop new therapies to control post transplant inflammation.
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Prof. Jesper Hjortdal (Aarhus University Hospital), who leads the VISICORT Clinical Study Group comments: Immune reactions (rejection episodes) towards transplanted corneal tissues are common and a rejection episode often results in failure of the corneal graft. In the UK study follow-up was missing for 10-20% of the operated patients, which actually is superior compared with many other registries. Smaller, single clinic studies have been in-line with the UK Transplant Registry Study, although a tendency to lower rejection rates for EK was found in patients with Fuchs endothelial dystrophy (1,2). Prospective, longer-term studies extending beyond a 2-year follow-up are needed to further evaluate risk factors for immune reactions. VISICORT will provide such data within the coming years.

Refs:
1. Hjortdal J, Pedersen IB, Bak-Nielsen S, Ivarsen A. Graft rejection and graft failure after penetrating keratoplasty or posterior lamellar keratoplasty for fuchs endothelial dystrophy. Cornea. 2013 May;32(5):e60-3.
2. Pedersen IB, Ivarsen A, Hjortdal J. Graft rejection and failure following endothelial keratoplasty (DSAEK) and penetrating keratoplasty for secondary endothelial failure. Acta Ophthalmol. 2015 Mar;93(2):172-7.

The Medical Times and the Irish College of Ophthalmologists announce commencement of recruitment to VISICORT’s Irish trial

The Medical Times and the Irish College of Ophthalmologists announce the commencement of recruitment for the VISICORT trial.

First VISICORT Plenary Meeting

The first plenary meeting of the VISICORT consortium took place last week on October 27th. The meeting took place on the campus of NUI Galway, and each of the consortium partners was represented at the event. Thanks to the huge efforts of everyone involved, work is progressing very well and we are on target to deliver a project which will deliver significant impact for the field. A big thank you to all who took part in a very successful event, and we look forward to meeting again in Berlin in April 2015.

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