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