The cells that protect the surface of the eye's cornea can be damaged through disease or injury, to the extent that vision is impaired. Limbal stem cell allograft transplantation involves the grafting of stem cells that have been taken from donor eyes and grown in tissue culture, with the aim of improving vision and other symptoms such as eye irritation and dryness

The National Institute for Health and Clinical Excellence is examining tissue-cultured limbal stem cell allograft transplantation and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about tissue-cultured limbal stem cell allograft transplantation.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the preliminary recommendations
  
• the identification of factual inaccuracies
  
• additional relevant evidence.

Note that this document is not the Institute's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that the Institute will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  
• The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprogrammemanual).

Closing date for comments: 31 January 2007
Target date for publication of guidance: April 2007

Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.

Current evidence on the safety and efficacy of tissue-cultured limbal stem cell allograft transplantation does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.

Clinicians wishing to use tissue-cultured limbal stem cell allograft transplantation should take the following actions.

? Inform the clinical governance leads in their Trusts.

? Ensure that patients understand the uncertainty about the procedure's safety and efficacy, and provide them with clear written information. In addition, use of the Institute's information for patients ('Understanding NICE guidance') is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]

? Audit and review clinical outcomes of all patients having tissue-cultured limbal stem cell allograft transplantation (see section 3.1).

Further research on the procedure and long-term outcomes will be useful. The Institute may review the procedure upon publication of further evidence.

The procedure is used to treat limbal stem cell deficiency (LSCD). The limbus is the part of the eye where the cornea joins the sclera, and where the conjunctiva, which covers the sclera, ends. Undifferentiated epithelial cells are produced at the limbus and differentiate to become conjunctival and corneal epithelial cells. Failure of this process can result in a variety of serious and intractable disorders of the ocular surface, including loss of corneal transparency, which impairs vision. Limbal stem cell production may be damaged by various disease processes or chemical injury.

A healthy conjunctival and corneal surface can be restored by the use of ocular lubricants, but surgery is required in severe cases. Surgical techniques include amniotic membrane grafts, which may be combined with grafting of uncultured limbal stem cells and, where necessary, subsequent corneal grafting.

Most studies reported efficacy outcomes relating to resolution of LSCD in terms of corneal re-epithealisation and/or resolution of corneal vascularisation, corneal conjuctivisation, inflammation/scarring, pain, photophobia and corneal opacity. Definitions of success varied between studies. Resolution of LSCD was achieved following tissue-cultured limbal stem cell transplantation in between 70% (7/10) and 100% (13/13) of eyes.

In one case series, complete epithelialisation of the corneal surface was achieved in 8 out of 10 eyes by the time the amniotic membrane had dispersed. In another series, corneal epithelialisation was achieved in 46% (6/13) of eyes at final follow-up (length of follow-up not stated). In a case series of 10 patients, corneal epithelialisation was incomplete; corneal epithelial defects (one of them persistent) were reported in two patients.

The case series reported visual acuity following tissue-cultured limbal stem cell allograft transplantation in between 40% (4/10) and 77% (10/13) of eyes, although concomitant surgery to improve vision was undertaken in some patients. For more details, refer to the sources of evidence (see Appendix).

Bacterial infection following tissue-cultured limbal stem cell allograft transplantation occurred in 7-15% of eyes (1/13 and 2/13). In one case series, corneal perforation occurred in 31% (4/13) of eyes.

Post-procedural development of glaucoma requiring trabeculotomy was reported in 1 of 13 eyes (7%) in one case series (follow-up not stated). For more details, refer to the sources of evidence (see Appendix).

The Specialist Adviser stated that theoretical adverse events may include may include infection by diseased donor tissue, and potential failure of the corneal epithelial stem cell supply in the donor, although this risk was thought to be very small.

This guidance requires that clinicians undertaking the procedure make special arrangements for audit. The Institute has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

• 'Interventional procedure overview of tissue-cultured limbal stem cell allograft transplantation', October 2006.