Photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A for keratoconus (interventional procedures consultation)
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Interventional procedure consultation document
Photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A for keratoconus
Keratoconus is a degenerative condition that usually involves both eyes. It affects the shape of the eyeball and causes blurred vision and light sensitivity. Wearing spectacles or contact lenses can help some people who have this condition. Photochemical corneal collagen cross-linkage is an outpatient procedure. First a local anaesthetic is given in the form of eye drops. Then riboflavin (vitamin B2) drops are applied to the eye, and it is exposed to ultraviolet light. This procedure aims to stabilise the outer coating of the eyeball, called the cornea, with the intention of preventing further changes to its shape.
The National Institute for Health and Clinical Excellence (NICE) is examining photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A for keratoconus and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’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 photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A for keratoconus.
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 provisional recommendations
- the identification of factual inaccuracies
- additional relevant evidence, with bibliographic references where possible.
Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.
The process that NICE 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- The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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 NICE website (www.nice.org.uk/ipprogrammemanual).
NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.
Closing date for comments: 28 July 2009
Target date for publication of guidance: November 2009
1. Provisional recommendations
1.1 Current evidence on the safety and efficacy of photochemical corneal collagen cross-linkage using riboflavin and ultraviolet A (UVA) for keratoconus is inadequate in quantity and quality. Therefore this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
1.2 Clinicians wishing to undertake photochemical corneal collagen cross-linkage using riboflavin and UVA for keratoconus should take the following actions.
- Inform the clinical governance leads in their Trusts.
- Ensure that patients and their parents/carers understand the uncertainty about the procedure’s safety and efficacy, including the possibility of side effects in the long-term, and that the procedure may need to be repeated, and provide them with clear information. In addition, the use of NICE’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 photochemical corneal collagen cross-linkage using riboflavin and UVA for keratoconus (see section 3.1).
1.3 The procedure should only be carried out on patients with progressive keratoconus and corneal thickness greater than 400 micrometres.
1.4 Photochemical corneal collagen cross-linkage using riboflavin and UVA for keratoconus should only be carried out by ophthalmologists with expertise in the management of corneal disease and specific training in the use of ultraviolet light.
1.5 NICE encourages further research into photochemical corneal collagen cross-linkage using riboflavin and UVA for keratoconus. Research should take the form of studies that allow comparison with the natural history of the disease, and should define patient selection criteria based on estimated risk of disease progression. Outcomes should include measurement of visual acuity, topographic assessment of corneal stability, prevention of progression to transplant, and long-term safety. NICE may review the procedure on publication of further evidence.
2. The procedure
2. Indications and current treatments
2.1.1 Keratoconus is a progressive disease in which the corneal surface becomes thinner and begins to bulge into a cone-like shape. This causes refractive error and is often associated with astigmatism, both of which lead to visual impairment.
2.1.2 In mild to moderate keratoconus, the use of spectacles or contact lenses is sufficient to correct visual acuity. In severe cases, rigid gas-permeable contact lenses may be worn. Penetrating keratoplasty or implantation of corneal ring segment inserts may be required for severe progressive keratoconus.
2.2 Outline of the procedure
2.2.1 The aim of the procedure is to induce cross-linkage between the corneal collagen fibres, increasing the stability of the cornea and halting the progression of keratoconus. Before the procedure, progressive keratoconus should be demonstrated by corneal topographic measurements and demonstration of reduced visual acuity.
2.2.2 This is an outpatient procedure which is done using topical anaesthesia. The epithelium is abraded with a blunt spatula with the aim of facilitating penetration of riboflavin into the corneal tissue. Riboflavin eye drops are frequently applied to the corneal surface during exposure to UVA radiation lasting approximately 30 minutes. A slit lamp may be used to monitor the amount of riboflavin penetration.
2.2.3 Postoperative care usually involves analgesics or artificial tears and the use of antibiotic ointment until re-epithelialisation. The procedure may need to be repeated if the disease progresses despite treatment.
| Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/IP724overview |
2.3 Efficacy
2.3.1 A preliminary report from a randomised controlled trial (RCT) of 49 patients (66 eyes) treated by corneal collagen cross-linkage using riboflavin and UVA or no treatment reported a non-significant improvement in best spectacle-corrected visual acuity from baseline to 12-month follow-up (n = 20, p = 0.07). Keratometric measurements showed significant stabilisation in the treatment group compared with progression of keratoconus in the control group.
2.3.2 A case series of 130 patients (241 eyes) reported that 53% of patients had an improvement of at least one line in best corrected visual acuity (BCVA) and 20% had a stable BCVA at 1-year follow-up (absolute figures not stated). The figures after 3 years were 59% and 29% respectively (based on 33 eyes). A case series of 22 patients (23 eyes) reported regression of keratoconus in 70% (16/23) of eyes, with an average reduction of 2.01 dioptres (a measure of the refraction of the cornea) (95% confidence interval 1.23 to 3.07, p = 0.001).
2.3.3 The Specialist Advisers listed key efficacy outcomes as measurements of refractive and keratometric corneal stability showing that keratoconus is not progressing, and reduction in refractive error or of corneal power.
2.4 Safety
2.4.1 A case report described a patient diagnosed with herpes simplex virus infection of the eye 5 days after treatment. The ulcer re-epithelialised following 2 days of oral antiviral and anti-inflammatory treatment. After 2 months, there was mild corneal opacity but the uncorrected visual acuity had recovered to the preoperative value.
2.4.2 The case series of 130 patients (241 eyes) reported neurodermatitis in two patients who were being treated concurrently with systemic treatment for keratoconus (not otherwise described) at 18- and 21-month follow-up.
2.4.3 The case series of 22 patients (23 eyes) reported slight transient stromal oedema after 3 days in most patients (absolute figures not stated).
2.4.4 The RCT of 49 patients (66 eyes) reported a transient inflammatory reaction in one patient 2 days after the procedure. Another patient developed a subepithelial, paracentral infiltrate 3 days after the procedure (associated with premature rigid contact lens use).
2.4.5 The Specialist Advisers considered theoretical adverse events to include corneal scarring, keratocyte damage, corneal endothelial cell damage, corneal haze, infection, recurrent corneal erosion and the need for repeat surgery.
3 Further information
3.1 This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE 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.
3.2 For related NICE guidance see www.nice.org.uk.
Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
July 2009
Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.
It is the responsibility of consultees to accurately cite academic work in order that they can be validated.