 Latest
News. Collagen crosslinking for keratoconus – halting progression
More
and more evidence is
accumulating that keratoconus
progression is halted
by corneal collagen
cross-linking treatment. This means that our traditional approach
to keratoconus treatment is likely
to change.
 In New Zealand, a
country with a high
prevalence of keratoconus and the highest reported
rate of corneal transplant
surgery for keratoconus
in the world1, collagen cross-linking has the
potential to become a
very important sight-preserving
treatment.
Properly known as corneal
collagen cross-linking
with riboflavin (“C3R”, “CCL” and “CXL” are
shorthand terms),
the procedure causes
stiffening of the
cornea so that it resists
further deformation.
In keratoconus, the cornea weakens, thins
and steepens with
development of irregular
astigmatism. C3R causes
enhanced cross-linking between
collagen microfibrils
in the cornea, and
between and within
the molecular building blocks of these microfibrils.
This is achieved by
applying
non-toxic riboflavin
(vitamin B2) to the
cornea to act as a photosensitiser, then using
a measured
dosage of Ultraviolet-A
radiation (UVA) to
generate free radicals within the cornea with
chemical
cross-links resulting.
 In practical terms
for the patient, the
procedure is straightforward
and comfortable. Local
anaesthetic drops are
given before removal
of the central 8-9mm
of corneal epithelium.
Riboflavin solution
is then applied for 30 minutes to saturate
the corneal stroma
before the UV-A treatment
is carried out using
a precisely calibrated
instrument such as
the UV-X system, again
for 30 minutes. Aftercare is much
the same as for PRK
excimer laser treatment,
with a bandage contact
lens applied and topical treatment to improve
comfort and
epithelial healing
over the next three
days.
The increased cross-linking
within the cornea leads
to a stiffening effect,
akin to the corneal
stiffening that occurs
with natural ageing. The biomechanical
strength of human cornea
may be increased by
a factor of 3 or more2.
This increased corneal
rigidity appears to
be responsible for
slowing or halting of corneal ectasia.
 The
C3R process, using
riboflavin solution
combined with UVA exposure,
was developed in Germany
from 1993 onwards
with the first patients
treated in 1998. The
treatment has been
steadily gaining momentum as clinical
results have become
available with clinical
trials continuing in
several centres around the world
and the FDA in the
USA recently approving
a trial of C3R.
Published
evidence uniformly
shows no progression
of keratoconus in the follow-up period
3-5. For example,
in the Dresden study
of 60 eyes with 5 years
follow-up, no eyes
had progression and about half of
eyes demonstrated some
flattening of keratometry
values3. A slight mean
improvement of 1.4 lines in best
corrected visual
acuity was also found.
Early results of
a randomised trial
in Melbourne, reported
at the RANZCO Congress
in November 2007,
also showed flattening
of steepest keratometry
values with a small
improvement in best
corrected visual
acuity5. The untreated
control eyes in the
same 3 month period showed
steepening of keratometry
(mean 1.45D).
C3R
is also likely to
have a complementary
effect with intrastromal
corneal implant surgery
(Intacs, Kerarings).
The procedures have
been performed both
simultaneously and
with intrastromal rings preceding C3R
by a few months (C3R
potentially “locking
in” the flattening effect of intrastromal
rings). Studies thus
far suggest additive
effects6,7.
Potential
candidates for C3R
are those with demonstrated
progression of keratoconus
or other corneal ectasias (pellucid
marginal degeneration,
iatrogenic cases).
A minimum corneal
thickness of 400 microns after
epithelium removal
is a requirement
to protect the endothelium from potentially
toxic UVA levels8.
This is measured before treatment is commenced – if
the cornea is too
thin, a hypotonic
riboflavin solution
may be applied to
cause corneal swelling, sufficient to enable
safe treatment. No
sight-threatening
side effects have
been reported from worldwide
experience.
In the
last issue of (NZ
Optics March 2008),
a speaker at the
Global Keratoconus
Congress in Las Vegas,
Dr Kenneth McCandless,
talked of a paradigm
shift in our approach
to the management
of keratoconus, with
intrastromal corneal
implants being the
preferred choice for contact lens intolerant
patients, resulting
in deferment of, or
avoiding the need for,
corneal
transplant surgery.
The exciting twin developments
of C3R and intrastromal
implants, together
with their excellent
safety profile so far,
may mean that the standard
treatment paradigm shifts again – from
intervention following contact lens intolerance
to intervention much
closer
to initial diagnosis
with demonstrated
progression. The outlook for treatment of keratoconus
and
other ectasias is
brighter now than
ever before.
*
Dr Adam Watson is
a partner at Eye Institute.
He specialises in corneal,
cataract, oculoplastic and
refractive surgery.
Adam divides his time
at Eye Institute between the Remuera
clinic and Eye Institute’s clinic on the
North Shore. He also
has a public position
working as a consultant surgeon for Counties
Manukau
DHB.1.
New Zealand, Auckland – Published
in New Zealand Optics Magazine April
2008
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