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CXL
* Corneal collagen-
cross-linking for
veterinarians
* Collagen Cross-Linking
Dr Frank FAMOSE – DESV-ophta
frankfamose@gmail.com
Toulouse October 6th, 2016
Collagen reticulation by cross-linking
A natural…
or industrial… … or medical process
Collagen reticulation
Anti-infectious effects
Keratocytes apoptosis
The photochemical process
The Dresden protocol
A recent breakthrough…
The CXL in human ophthalmology
Corneal ectasia:
Progressive keratoconus
Post-LASIK ectasia
Pellucid marginal deg.
Infectious keratitis:
PACK-CXL
Bullous keratopathy
The CXL in veterinary ophthalmology
Infectious keratitis
(dogs, cats, horses)
Bullous keratopathy
(dogs)
Keratomalacia
« corneal melting »
MMP imbalance
Perforation
Antibiotics
& anticollagenases
Tectonic surgery
CXL
Results*
8 dogs 10 cats
*Accelerated cross-linking
D1 D31
8/8 dogs – 10/10 cats 2/8 dogs – 3/10 cats
Corneal vascularization
Corneal scar
D1 D31
8/8 dogs – 10/10 cats
Discussion
Clinical and
pain
improvement
Direct effects of UVA
Free oxygen radicals
Physical changes within
the cornea
Biological corneal
response
Adverse effects ?
Infections
Herpesvirus reactivation
Endothelial alterations
In humans
No adverse effects attributable
to the treatment
Ulcerative keratitis in Horses
(Dr Hellander-Edman)
9 cases Ulcerative keratitis
(Dresden protocol)
8 good results (1-3 months)
1 enucleation (fungal
keratitis)
Worse than dogs and cats ?
Corneal /epithelial thickness
Depth of infection
Low power UVA
RF administration?
Protocol modifications
Epithelium RF distribution UVA irradiation
Standard or accelerated ?
Standard
3 mW/cm²
30 minutes
« Flash »
30 mW/cm²
3 minutes
5,4 J/cm²
Total duration
ab. 1h20
Total duration
ab. 40 min
Same biological
effects ?
Same energy
level
Iontophoresis
Use of a low intensity
continuous electric current
to enhance the penetration of
a ionized substance
through a biological tissue
Iontophoresis
Same therapeutic
effects (keratitis)
Bullous keratopathy
Endothelial alterations
Corneal edema
Bullae and epithelial ulcers
« Epi-off »
Stromal
compaction
UVA irradiation
Hyperosmotic
topical drugs
RF +
Dextran 20 %
9 mW/cm²
10 minutes
Bullous keratopathy
Results
Epithelial healing (<1 sem)
Conclusion
Main indication : infectious keratitis
2 main constraints
- High fluence
- Minimal corneal thickness
Secondary indication: Bullous keratopathy
Merci
ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

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ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Editor's Notes

  1. As you know, melting keratitis is a serious condition which is considered as an ocular emergency due to the high risk or corneal perforation. The melting of the cornea is due to metalloproteinase imbalance in relation with infectious or not infectious conditions. When the medical treatment, based on antibiotics and anticollagenases doesn’t succeed, surgery is indicated for tectonic purposes. Corneal collagen cross-linking is used for the treatment of infectious or melting keratitis in humans for some years and more recently for CN, CT and horses.
  2. Brachycephalic: dogs 18/32, cats 13/35. Failures: 5/25 with standard protocol. 3/43 w accelerated protocol. But ulcers in standard prot studies larger.
  3. Collagen cross-linking has been primarily developed for the treatment of human progressive keratoconus and all the protocols used are adapted from the conventional protocol. This consists in instillation of riboflavin during 30 minutes after removal of the epithelium and UV exposition for 30 minutes à 3 mW/cm². Modifications of this protocol have been proposed for 3 aims : preserving the epithelium, enhancing the riboflavin impregnation or shortening the exposition time by increasing the UV light intensity. Iontophoresis is a way of enhancing riboflavin impregnation.
  4. The principle of iontophoresis is to increase the penetration of a ionized substance through a tissue by the application of a constant electric current. It has been used for first time in ophthalmology in the beginning of the 20th century. Many studies have been conducted since 1990 for the delivery of many drugs in the eye (like steroids and so on). The first use of iontophoresis for riboflavin delivery was published recently for the treatment of keratoconus. For the moment, no veterinary clinical use of ionto has been described and no data for keratitis treatment is available.
  5. The iontophoresis device we have used has three parts : The corneal electrode is maintained on the corneal surface by suction and is filled with riboflavin till the grid is covered. The generator applies a constant current between the electrodes The return electrode which is connected to a needle inserted under the frontal skin.
  6. But in second step, we can imagine that if iontophoresis could enhance penetration of riboflavin, this process could work for other therapeutic agents like antibiotics. There’s a big work to do in this field and this is another story…
  7. Thank you for your attention. I’ll be happy to answer to any question.