Download Collagen Crosslinking

Collagen Crosslinking

Idea:
The corneal collagen crosslinking procedure combines riboflavin (vitamin B2), which is a naturally
occurring photosensitizer found in all human cells, and ultraviolet A (UVA) light to strengthen the
biomechanical properties of the cornea. Although there may also be a slight flattening of the cornea,
the most important effect of collagen crosslinking is that it appears to stabilize the corneal curvature
and prevent further steepening and bulging of the corneal stroma. There is no significant change in
the refractive index or the clarity of the cornea.

Indications:
1) Prevent the progression of keratoconus and ectasia
following corneal refractive surgery
2) corneal melts & infectious keratitis: to strengthen a
collagenolytic cornea while UVA irradiation
eliminates the infectious agent
3) corneal edema e.g. bullous keratopathy, Fuchs
endothelial dystrophy

Contra-indications:
1)
2)
3)
4)
5)
6)
7)

Corneal thickness of less than 400 microns
Prior herpetic infection
Concurrent infection
Severe corneal scarring or opacification
History of poor epithelial wound healing
Severe ocular surface disease (ex. dry eye)
Autoimmune disorders
Physical principle:
Riboflavin alone has no crosslinking effect. Its function as a
photosensitizer is to serve as a source for the generation of
singlet oxygen and superoxide anion free radicals, which are
split from its ring structure after exitation by the UV
irradiation and which then lead to physical crosslinking of the
corneal collagen fibers.

In the presence of riboflavin,
approximately 95% of the UVA
light irradiance is absorbed
superficially in the anterior 300 µm
of the corneal stroma. Therefore,
most studies require a minimal
corneal thickness of 400 µm after
epithelial removal in order to
prevent
corneal
endothelial
damage. Thinner corneas may be
thickened
temporarily
with
application
of
a
hypotonic
riboflavin formulation prior to UVA.
treatment
Technique:
Corneal collagen crosslinking has
been
used
successfully
in
combination with other treatment
methods, such as intrastromal
corneal ring segments, CK, and
excimer laser photoablation
1) corneal epithelium is removed to increase UV
penetration
2) 30-minute application of riboflavin (0.1% diluted in 20% dextran) every 2 minutes
3) 30-minute UVA treatment (370 nm; 3 m W/cm2 irradiation), with concomitant administration
of topical riboflavin

Complications:
1)
2)
3)
4)
5)
6)
delayed epithelial healing,
corneal haze (may be visually significant)
decreased corneal sensitivity
infectious keratitis,
persistent corneal edema
endothelial cell damage.

Trans-epithelial CXL:
A cross-linking procedure without epithelial removal would likely be less painful
than one with the large diameter epithelial removal described above and would be ideal
if it efficiently stabilized keratectasia.
Several substances have been used to loosen the tight junctions of the epithelial layer
and thus increase the penetration of riboflavin. One is a riboflavin solution containing
benzalkonium chloride (BAK), the most commonly used preservative in ophthalmic
medications. BAK is also a tensioactive substance, surfactant or an active surface agent
that changes the surface tension value, and hence would facilitate the penetration of
substances through the epithelium.