Collagen cross linking is used for treatment of keratoconus.

1. The Cornea
 The anterior 1/6 of the outer coat.
 Acting as a covering lens.
 Avascular and transparent.

2. The Cornea

3. BIOCHEMISTRY
EPITHELIUM
 High activities of enzymes of glycolysis.
 Kreb’s cycle and ATPase pump.
 High concentration of acetyl choline
and choline esterases .

4. BIOCHEMISTRY
STROMA
 Low enzymatic activity
 Collagen fibrils.
 Glycosaminoglycans occupy
the interfibrillar space.

5. ENDOTHELIUM
 Assessment of function
1-Pachymetry
Measurement of
corneal thickness
2-Specular microscopy
Studying number and
shape of cells
BIOCHEMISTRY

6. 3-Flurography
Topical fluorescin drops

7. Keratoconus
The disease is characterised by thinning and conus like protrusion of
the cornea.

10.  In progressing / advancing cases of Keratoconus rigid
contact lenses can improve visual acuity, yet they can
not stop the process.
 corneal transplantation (penetrating keratoplasty) to
achieve better vision.
 Recently a new procedure has been developed which is
supposed to stop the progression of keratoconus.

11.  A non-invasive treatment C3-R® (corneal collagen cross-
linking riboflavin) (CXL) treatment has been proven to
strengthen the weak corneal structure.
 This method works by increasing collagen cross-linking,
which are the natural "anchors" within the cornea. These
anchors are responsible for preventing the cornea from
bulging out and becoming steep and irregular (which is the
cause of keratoconus).
 This procedure stops the progression of the Keratoconus
and therefore the need for penetrating keratoplasty
could be significantly reduced in the future.

12.  The first landmark article on this therapy, published 5
years ago, demonstrated clinically significant stiffening
of the corneal stroma after CXL in patients with
keratoconus.
 reporting a mean keratometric regression of 2 D over
the course of 23 months after 30 minutes of exposure
to ultraviolet A (UVA) light and topical application of
riboflavin.
 Potential applications of the CXL technique include the
treatment of keratoconus, post-LASIK ectasia and
refractory, non healing corneal ulcerations.

13. Crosslinking Pharmacokinetics
 Experimental evidence has shown that the
photosensitizer riboflavin and UVA lead to corneal
tissue strengthening by increasing collagen covalent
bonds, similar to photopolymerization in polymers.
 CXL induces an increase in the formation of intra- and
interfibrillar covalent bonds by photosensitized
oxidation, which leads to a biomechanical stabilization
of the cornea.
 The basis of the idea came from scientific evidence
that the natural crosslinking effect of glucose increases
corneal resistance in young diabetic patients.
Interestingly, in these conditions, keratoconus rarely
occurs.

19. To stabilize the cornea.
To stop the progression of the disease.
 What are the main goals of the
UV - cross linking treatment with respect to the
named indications?

20.  The Corneal Cross Linking is relatively easy and low in
costs.
 The main structure of the corneal tissue (stroma)
consists of single collagen fibers which are linked -
inter connected.
 The treatment is based on a significant stiffening of
the corneal stroma due to photochemical cross linking
of the single collagen fibers.
 Therefore the single fibers form a "denser network"
which leads to an increase in the overall stability of the
cornea.

21. • Which diagnostic tools can be used to rate the
efficacy of the treatment?
  Corneal topography
  Best-corrected visual acuity
  Corneal thickness
  Slit lamp examination of keratoconus level
and classification

22. • What are the treatment steps ?
 Local anaesthesia.
 Manual epithelial removal 6-8 mm OR 30 seconds of
application of 20% alcohol.
 Drop riboflavine 0.1% solution in the glucose polymer
Dextran T500 20% solution As a photosensitizer,
(every 3 min for approx. 30 min)
 Observe clear fluorescence within the anterior chamber
seen by slit lamb (blue light).
 Irradiate the cornea with UV-X for 30 min.
 Drop riboflavin solution every 5 min.
 Apply every 2 minutes BSS to moisten the cornea.
 The treatment must always be visually controlled

25. • Exclusion criteria:
 Hazy cornea
 Pachymetry <400μ
 Age >40 and <18 years
 Pregnancy or Nursing
 Previous anterior segment surgery
 Systemic Collagen pathology
 Associated Corneal pathology
 Severe dry eye

26. • How do I check the light intensity ?
The nominal value for correct
irradiance is
3.0  0.3 mW/cm² (2.7 – 3.3
mW/cm²).

27. • How do I have to position the patient ?

28. • How much UV – light gets into the eye ?
0.65 J/cm2
70 J/cm2
70 J/cm2 7.7 J/cm2
Damage thresholds
0.46 J/cm2 (9 %)
0.33 J/cm2 (7 %)
0.14 J/cm2 (2.1%)
0.12 J/cm2 (1.9%)
Radiant exposures
5.4
J/cm
2

29. • Where do I get Riboflavin ?

30.  provided that the time of application of riboflavin is
increased and the presence of riboflavin in the anterior
chamber is confirmed by the presence of a yellow flare
during slit lamp examination prior to the application of
UVA light.
 Using a UV-X radiation system (Peschke Med,
Huenenberg, Switzerland).
 370 nm UVA light is applied at a 5-cm working distance
for 30 minutes using a 3 mW/cm2 irradiance
(approximately 5.4 J/cm2)

31. UVA light is applied in precise amounts using a
specialized goggle with LED lights

32.  After the treatment, an antibiotic eye drop is applied,
and a bandage contact lens is fitted to the corneal
surface until re epithelialization.
 Combination of a steroid and antibiotic drop is
prescribed.
 During the follow up of eyes so far treated with
collagen cross linking very few of the patients showed
any more progression

34. Clinical Side Effects
 To date, no remarkable clinical side effects or
complications have been noted during clinical trials
and studies performed at multiple centers.
 longer follow up data is needed.

35.  Mild transient edema is usual in eyes, with a mild
cotton-like hazy appearance within the corneal stroma,
which usually resolves after 4 to 6 weeks with
treatment.
 A delay in re epithelization had been noted in an eye
receiving corticosteroid medication during the period
of epithelization and bandage soft contact lens wear.
 Following withdrawal of the corticosteroid medication,
re epithelization was complete within 24 hours