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Markus Kohlhaas University Eye Hospital Dresden
(Dir.: Prof. Dr. med. Lutz E. Pillunat)
Collagen cross-linking for the treatment of
keratoconus or keratectasia
Keratoconus?
Cause still "unknown"?• Enzymatic changes in
the epithelium with increased expression of lysosomal and proteolytic enzyms
• Changes of the stromal matrix (Keratan- and Dermatansulfate)
• Genetic• Contactlenses?• Eye-rubbing?
Treatment Options for Keratoconus
• Glasses• Contactlenses• Epikeratophakia• Lamellar Keratopl.• Pen. Keratoplasty• Intacs• Collagen cross linking
with Riboflavin/UVA light
Cross-linking for Keratoconus(Clinical Trial, Amsler 1 - 4))
• 128 eyes, mean age 30.59+/-10.16 years (13 to 58)
• K-Values between 41.7 and 72.47 D
• All showed progression of keratoconus
• Topical Anesthesia• Epithelium abrasio 8-9 mm• Riboflavin drops every 5 min
and 30 min radiation with 365 nm UVA-light
1. Combined application of UVA and riboflavin
riboflavin (vit. B2) Ultraviolet irradiation
2. Production of oxygen radicals
O2-
3. Induction of collagen cross-links
-CH2-CH2-CH2-CH = N-CH2-CH2-CH2-CH2-
collagen fibril collagen fibril
C
C
C
H2C
H OH
H OH
H OH
O POH
OH
O
H2C
N
NNH
NH3C
H3C
O
O
-
Stress-Strain Diagram
• 40 porcine eyes: 20 were treated with Riboflavin/UVA-light (3mW/cm²; 30 min) and 20 eyes served as control
• From each eye 2 flaps, each 200 µm thick and 9 mm in diameter, were taken and were cut into stripes, 5 x 7 mm in size
• The stress-strain behavior of the stripes was measured
0
200
400
600
800
1000
1200
0 2 4 6 8 10
Strain in %
Stre
ss in
10³
N/m
²
first treated flaps
first untreated flaps
second untreated flaps
second treated flaps
porcine cornea
Depth dependent effect Earlier studies showed:• Homogene Riboflavin
concentration throughout the cornea
• Increase of stiffness only depends on the intensity of the UVA-light
• Exponential decrease of radiation intensity follows the Lambert-Beer-Rule
• 65% of UVA-light is absorbed within the first 250 µm of corneal stroma, only 7 % reaches the endothelium
Therefore deeper structures, such as retina, lens and even the endothelium don‘t get damaged
Depth Dependant Keratocyte Loss• 38 rabbit eyes• Epithelium abrasio and
Riboflavin treatment• Exposure to UVA (370µm)
light with different intensities• Histological examination• Keratocyte loss and
apoptosis up to different depth, depending on the irradiance
• Keratocytes migrate back into the radiated zone from the periphery over time
1.5 mW/cm²
2.65 mW/cm²
4.0 mW/cm²
Cross-linking treatments (n=128) since 1999 (31.3.05)
0
5
10
15
20
25
30
35
1999 2000 2001 2002 2003 2004 2005
[ Year ]
[ Num
ber ]
Astigmatism after crosslinking
according to Amsler 1
17
28
2114
12
4
3
2
Visual acuity after crosslinking
according to Amsler 1
2
17
2620
3
1215
2
1
2
3
4
5
Astigmatism after crosslinking
according to Amsler 4
Visual acuity after crosslinking
according to Amsler 4
1
2
3
45
Astigmatism after crosslinking
according to Amsler 1-4
49
81
5739 32
178
6
Visual acuity after crosslinking
according to Amsler 1-4
47
7755
4432
16
8 6
Results after Cross-linking
• None of the patients showed progression
• In 81.7% a regression of the max. K-values of -2.87+/-2.56 D (0.18 to 9.97 D) could be seen
• The post surgery visual acuity rose by 1.4+/-2.04 lines
• No opacity of the lens• No loss of endothelial
cells
Keratoconus: OD 5 Years after Cross Linking
Further Indication (n=6)
• Keratectasia after Lasik• Rare but severe complication• Cause still unknown???
OS: Before Lasik, 9 Months after Lasik, 1 and 2 Years after Cross Linking
K-values before and after Lasik and after cross-linking
Summary• Modification of biochemical and biomechanical
characteristics of the cornea• The Riboflavin/UVA light causes an increase in
corneal stiffness of the anterior 200-250 µm• Deeper structures don‘t get damaged • The progression of keratoconus or keratectasia can
be stopped• The number of keratoplasties can be reduced• Easy / simple treatment with low costs
If there is progression, an early cross-linking treatment is recommended
Treats the cause, not only the symptoms
Thank you
for
your attention