The document discusses recent advancements in corneal collagen cross-linking (CXL) techniques aimed at treating progressive keratoconus and post-LASIK ectasia. It highlights the comparison between epithelium-on and epithelium-off CXL, as well as the efficacy of iontophoresis and modified protocols for thin corneas. Additionally, it emphasizes the need for aggressive treatment strategies in pediatric patients with keratoconus and the importance of further research for various CXL techniques, especially in cases of infectious keratitis.

1. Recent Updates In
Corneal Collagen
Crosslinking.
Dr. Amr Mounir.MD
Lecturer of Ophthalmology
Sohag University Hospital

2. Introduction:
 Corneal collagen cross-linking is a technique
which uses UV light and a photosensitizer to
strengthen chemical bonds in the cornea.
 The goal of the treatment is to halt progressive
and irregular changes in corneal shape known as
ectasia.

3. Corneal collagen cross-linking techniques
were developed in Europe by researchers at
the University of Dresden in the late 1990's

4. Now, CXL is
considered as the
main treatment
option for patients
with progressive
Keratoconus and
post Lasik ectasia

5. After practicing CXL for several
years. Refinement becomes a
must.

6. Recent advances and debates
about CXL are needed to
discussed

8. Epi-On Versus Epi-Off

9. Epithelium-Off vs. Epithelium-
On CXL
One of the big questions is whether epithelium-on
CXL can provide similar results to crosslinking
procedures where the epithelium has been
removed (Epi-off CXL)
Advantages of epithelium-on CXL include reduced
risk of infection, less corneal haze and fewer
delays in epithelial healing.

13. Due to Epi-off complications
….Epi-on still in mind

14. How to increase efficacy of Epi-on
??
Iontophoresis
Enhanced Riboflavin solutions

15. Iontophoresis

16.  Iontophoresis consists of the transfer of molecules, with an
ionic charge, inside the tissues to treat, thanks to a low
intensity electric field.
 Iontophoresis increases the penetration power of special type
of riboflavin into the underlying epithelium with increase
efficacy of Epi-on CXL

17.  The mid-term results (12-18 months) available in scientific
literature (Bikbova et al., Acta Oftalmologica; Vinciguerra et
al., JRS; Mastropasqua et al., EUCORNEA and ESCRS
Congress 2014) show how iontophoresis is an efficacious
technique in stabilizing progressive keratoconus (reduction
of Kmax, no variation in corneal thickness in the follow-up
period) with a moderate inflammatory activation and no
cases of haze in the treated patients.

18. Enhanced Riboflavin solutions

19. Enhanced Riboflavin
solutions
To increase Riboflavin penetration to
the corneal epithelium
Done by increase in riboflavin
concentration or using substances
increase epithelial disintegration

22. Customized Crosslinking

23. Customized Crosslinking to
Reshape the Cornea
Conventional CXL achieves this effect by
uniformly stiffening the central 9mm of the
anterior stroma.
Customized UVA illumination patterns will
allow surgeons to focally stiffen the
weakest region of the cornea rather than
the conventional approach of uniformly
stiffening the entire central cornea.

24. The Finite Element Method (FEM)

27. Photorefractive intrastromal cross-
linking (PiXL)
The device delivers specific light
patterns to the cornea based on a
patient’s topographic data.
 Used for refractive purposes.

29. CXL at Slit lamp
The C-Eye device
will allow for the
treatment of corneal
infections at the slit
lamp.

33. Antimicrobial resistance
 The graphic shows that by
2050, the WHO expects
that more people will die
due to antibiotic resistance
than to cancer and diabetes
combined.
 PACK-CXL kills bacteria
irrespective of their
antibiotic resistance.

34. Corneal collagen cross-linking
(CXL) in thin corneas

35. In the conventional CXL protocol,
A minimum de-epithelialized corneal
thickness of 400 μm is recommended to
avoid potential irradiation damage to the
corneal endothelium

36. The modified CXL protocols
In advanced keratoconus, stromal
thickness is often lower than 400 μm, which
limits the application of CXL in that
category So, modified CXL is needed.

37. Solutions
Power
Thickness
Time
Riboflavin
concentration

38. The modified CXL protocols for
thin cornea
Hypoosmolar riboflavin solution:
- The deepithelialized cornea can swell to double its normal
thickness when irrigated with a Hypoosmolar solution.
- The 0.1 % dextran-free Hypoosmolar riboflavin was then
administered until the corneal thickness at the thinnest point
reached 400 μm, before the initiation of UVA irradiation.

39. The modified CXL protocols for
thin cornea
Transepithelial collagen cross-linking
- By adding the enhancers to help riboflavin penetrate to the
corneal stroma through the intact epithelium, CXL can be
performed without epithelial debridement (Transepithelial
CXL)
- Thinner corneas can be treated safer by Transepithelial
compared to the conventional CXL, since the endothelium is
better protected by UVA-filtering effect of the intact
epithelium.

40. The modified CXL protocols for
thin cornea
Custom epithelial debridement
technique
- In this modified CXL approach, 8.0 mm diameter of corneal
epithelium was removed; leaving a small, localized area of
corneal epithelium corresponding to the thinnest area over
the apex of the cone.
- The ability of the epithelium to absorb the UVA radiation may
lead to reduced CXL effect in the cone area and affect the
efficacy of the whole procedure. Long-term efficacy of this
modified CXL procedure with a larger number of patients
needs to be assessed.

41. The modified CXL protocols for
thin cornea
Contact lens-assisted collagen cross-
linking
A Soflens daily disposable soft contact lens of 90 μm thickness
immersed in isoosmolar riboflavin 0.1 % in dextran for
30 minutes, before it was applied onto the deepithelialized,
riboflavin-saturated cornea.
The riboflavin solution was instilled every 3 minutes. The pre-
corneal riboflavin film with contact lens created an absorption
medium in the pre-corneal space by artificially increasing the
thickness of the “riboflavin-filter

42. PACK-CXL for Infectious
Keratitis

45. Effects of PACK-CXL in infective
keratitis
 Cornea :
1- Increase the biomechanical strength of cornea
2- Stabilize and increase response of cornea to
digestive enzymes of pathogens.

46. Effects of PACK-CXL in infective
keratitis
Microorganism:
3- Interaction of the chromophore (riboflavin) with
the nucleic acids of the pathogen and inhibition of
replication.
4. Damage to the pathogen’s cell walls caused by
massive amounts of Reactive oxygen
species (ROS)

50. Evidence based research:

51. My experience
4 years old boy with infected corneal ulcer
with severe AC reaction due to trauma
The patient received topical fortified eye
drops and topical antifungal ( Voriconazole)
but without response
The decision was to use PACK-cxl as a last
option.

54. Result: No improvement

55. Conclusion
Theoretically, PACK-CXL is
effective in infective keratitis but
need further evidence based
research

56. Pediatric CXL

57. KERATOCONUS PROGRESSION
Most frequent in younger patients (< 18
years)
Risk of acute KC development (< 16 years)
 More significant and faster refractive and
pachymetric worsening in young patients
25 % progression with CXL

58. Pediatric Comorbidities
Vernal keratoconjunctivitis (VKC):
- Continued surface inflammation and the tendency
toward eye rubbing further accelerates keratoconus
progression and may lead to advanced disease in
young age.
- Many eyes with VKC demonstrate partial limbal
cell deficiency which may result in delayed epithelial
healing after standard CXL treatment.

59. Advices in pediatric CXL

60. 1- Don't wait for progression
Once diagnosed
must be
crosslinked

61. 2- Hit Hard
 TE CXL may be of limited
value especially in the
pediatric age
 Standard epithelium off
CXL is recommended in
pediatric eyes
 TE CXL is needed in thin
corneas
 Epi-off ???? Take care
endothelium and infection

62. 3- Frequent screening
25 %
progression with
CXL

63. 4- In ocular allergy
No eye rubbing
Don't do CXL
in active VKC

65. Home Message
 Epi-On CXL is less effective than Epi-Off CXL But the Latter
has more complications.
 Trials has been mad to increase efficacy of Epi-On CXL by
Enhanced Riboflavin solutions and iontophoresis.
 Customized UVA illumination patterns will allow surgeons to
focally stiffen the weakest region of the cornea not all the
cornea.
 Theoretically, PACK-CXL is effective in infective keratitis but
need further evidence based research.
 Pediatric CXL should be aggressive , don't wait for
progression and frequent screening is mandatory.

66. Thank you