NICE Guidelines on CXL
Photochemical corneal collagen
cross-linkage using riboflavin and
ultraviolet A for keratoconus and
keratectasia
Issued: September 2013
NICE interventional procedure guidance 466
Recommendations
1.1 Current evidence on the safety and efficacy of
epithelium-off CXL for keratoconus and keratectasia
is adequate in quality and quantity. Therefore,
this procedure can be used provided that normal
arrangements are in place for clinical governance,
consent and audit.
1.2 Current evidence on the safety and efficacy of
epithelium-on (transepithelial CXL, and the combination
(CXL-plus) procedures for keratoconus and keratectasia
is inadequate in quantity and quality. Therefore, these
procedures should only be used with special
arrangements for clinical governance, consent and audit
or research.
1.3 Clinicians wishing to undertake epithelium-on
(transepithelial) CXL, or the combination (CXL-plus)
procedures should take the following actions:
A.
Inform the clinical governance leads in their NHS trusts.
B.
Ensure that patients and their parents or carers understand
the uncertainty about the efficacy and safety of the
procedures in the long term and provide them with
clear information. In addition, the use of NICE's information
for the public is recommended.
C.
Audit and review clinical outcomes of all patients having
these procedures for keratoconus and keratectasia.
1.4 Patient selection for these procedures should
include assessment of corneal thickness and
consideration of the likelihood of disease progression.
1.5 The procedures should only be carried out by
ophthalmologists with expertise in managing corneal
disease and specific training in the use of ultraviolet
light or by appropriately trained staff under their
supervision.
1.6
NICE encourages further research into CXL using
riboflavin and UVA for keratoconus and keratectasia,
especially epithelium-on (transepithelial) CXL and the
combination (CXL-plus) procedures.
Details of the techniques used should be clearly
described.
Reported outcomes should include visual acuity, corneal
topography and quality of life.
Data on long-term outcomes for all types of CXL using
riboflavin and UVA for keratoconus and keratectasia would
be useful – specifically data about prevention of
progression to corneal transplantation and about repeat
procedures and their efficacy.
The Procedures
CXL was first developed in 1998 by Theo Seiler MD.
Epithelium-off CXL
Pre op drops, LA , Riboflavin A (0.1%) drops 1-5 min for 1530 min+/- BSS, AC Level, Lid speculum, Epithelium off, UVA
(365-370um) at 1-5cm distance from corneal apex for 30 min
BCL, Post op drops (Antibiotic +NSAIDs+/- Steroids)
Epithelium-on (transepithelial) CXL
CXL-plus
Intracorneal ring segment (ICRS) implantation
Photorefractive keratectomy (PRK)
Phakic intraocular lens (PIOL) implantation
How does it work?
The aim of corneal
crosslinking is to
strengthen the cornea
by increasing the
number of "anchors"
that bond collagen
fibers together.
(Diagram: Boxer
Wachler Vision
Institute)
What does it do?
Corneal crosslinking
strengthens bonds in
the stroma of the
cornea, which is the
layer from which tissue
is removed during
LASIK surgery
2007-Dr Brian Wachler
did CXL-Plus for Steve
who won Feb.2010,
Vancouver Winter
Olympic
U.S. Olympic bobsledding
champion Steve Holcomb
overcame a heart breaking
diagnosis of legal blindness
that threatened to rob him
forever of his lifelong dream of
winning an Olympic gold medal
Patient Selection, Indications and
Contraindications
Corneal collagen cross-linking eligibility criteria:
Baseline data collection by Mr Philip Jaycock
Please ensure that patients have Pentacam scans
and refraction with contact lenses out for:
i.
RGP’s: minimum 2 weeks
ii.
Soft: minimum 1 week
Inclusion criteria (evidence of progression):
i.
ii.
iii.
iv.
v.
vi.
vii.
>1.00 D change in refractive astigmatism, OR
>1 line loss of corrected distance visual acuity, OR
>1.50 D increase in central steep anterior keratometry
(Pentacam [K2] or other topography (eg. SimK), OR
>1.50 D increase in Kmax (Pentacam), OR
>0.50 D increase in steep posterior K2 (Pentacam), OR
>13 microns decrease in central or minimum corneal
thickness (Pentacam), OR
Previous LASIK with ectasia
NB. Comparison should be with baseline (not simply previous visit).
K2 = steep curvature in the central 3mm zone; there is no upper limit
of Kmax (steepest point over the entire scanned anterior corneal
surface).
Exclusion criteria:(Contraindications)
i.
ii.
iii.
iv.
v.
vi.
Active ocular surface disease (e.g. Severe Dry Eye)
Pachymetry at thinnest location (epithelium on) < 375
microns
Significant corneal scarring
A history of previous herpes simplex keratitis is a relative
contraindication. These patients may be given Acyclovir
cover
Poor epithelial wound healing
Autoimmune disorder
For patients referred at 1st presentation please attach evidence of
altered refraction or topographic changes indicating progression in
line with the inclusion criteria above + baseline Pentacam scan.
Efficacy and Safety (Consent Info)
Efficacy: (Outcomes)
1. Epithelium-off CXL: (meta-analysis data from systematic review)
1. Topography (maxK, meanK ,minK) 2. CVA & UCVA 3. Astigmatism 4.SE
5.central corneal thickness 6. IOP
2. Epithelium-off CXL in combination with other
interventions (CXL-plus):
1.CXL+ICRS & ICRS+CXL (48 eyes) 2.PRK+CXL (42) 3.CXL+PIOL (11)
3. Epithelium-on (transepithelial) CXL with or without
additional interventions (CXL-plus):
1.Epi-on CXL (51) 2.Epi-on CXL+ICRS (14) 3.ICRS+Epi-on CXL (21)
Efficacy and Safety (Consent Info)
Efficacy outcomes listed by specialist advisers:
1. Arrest of progression of keratoconus
2. Stabilization of corneal shape measured by;
Topography, refraction and keratometry,
refractive astigmatism, change in corneal
thickness, cone apex power, quality of life and
contact lens independence.
Efficacy and Safety (Consent Info)
Safety: (Complication or Adverse Events)
1. Infections: 8- cases , 4-resloved,1-VA reduce, 3-unknown
2. Sterile Keratitis with scarring /loss of
vision/needing keratoplasty in 3% (4/117): 2
patients reduced BCVA
3. Stromal Scar: 4-cases only 1 needed correction with lens
4. Corneal Oedema 24/12, Inflammation 2-3/52, Iris
atrophy and pigment dispersion.
5. Corneal melting -1 case , Perforation- 2 cases
Efficacy and Safety (Consent Info)
6. Corneal burn and ulcer- 3 cases
7. Corneal haze with diffuse subepithelial
opacification and paracentral thinning with
scarring- 1 case
8. Stromal Haze- 10/10 cases ICRS+CXL on same day &
ICRS+CXL after 6/12
(Temporary stromal oedema (70%), temporary haze (up
to 100%), and permanent haze (10%)
9- Anecdotal AE: delayed epithelial healing, bilateral corneal
infection, transient recurrent erosion syndrome,
perforation after procedure- 1 case
Committee comments
6.1 The Committee noted that these procedures may
be useful for some disabled people who have
keratoconus or keratectasia and who would need to
wear contact lenses, but are unable to do so.
6.2 The Committee noted that the primary aim of the
procedures is to stabilise vision by halting
progression of keratoconus or keratectasia but that
many of the studies reported improvement of vision
as a secondary outcome.
Committee comments
6.3 The Committee noted that CXL techniques and
precise treatment regimens are continuing to develop
and evolve.
6.4 The Committee noted commentary from a patient
group describing the serious impact that keratoconus
or keratectasia can have on employment and quality
of life. The Committee recognised the potential
benefits that these procedures might offer, if further
evidence supports their efficacy.
Questions?
Thank You
Mr Muhammad Asalm Razzaq
Locum Consultant Ophthalmologist,
NDDH, Barnstaple.