esvo_sferov_corneal-cross-linking_technique_and_veterinary applications_ frank-famose

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CXL * Corneal collagen- cross-linking for veterinarians * Collagen Cross-Linking Dr Frank FAMOSE – DESV-ophta [email protected] Toulouse October 6th, 2016

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Page 1: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

CXL*Corneal collagen- cross-linking for veterinarians

* Collagen Cross-Linking

Dr Frank FAMOSE – [email protected] October 6th, 2016

Page 2: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Collagen reticulation by cross-linkingA natural…

or industrial… … or medical process

Page 3: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Collagen reticulation

Anti-infectious effects

Keratocytes apoptosis

The photochemical process

Page 4: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

The Dresden protocol

Page 5: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

A recent breakthrough…

Page 6: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

The CXL in human ophthalmology

Corneal ectasia:Progressive keratoconusPost-LASIK ectasiaPellucid marginal deg.

Infectious keratitis:PACK-CXL

Bullous keratopathy

Page 7: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

The CXL in veterinary ophthalmology

Infectious keratitis(dogs, cats, horses)

Bullous keratopathy(dogs)

Page 8: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Keratomalacia« corneal melting »

MMP imbalance

Perforation

Antibiotics& anticollagenases

Tectonic surgery

CXL

Page 9: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose
Page 10: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Results*

8 dogs 10 cats

*Accelerated cross-linking

Page 11: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

D1 D31

8/8 dogs – 10/10 cats 2/8 dogs – 3/10 cats

Corneal vascularization

Page 12: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Corneal scar

D1 D31

8/8 dogs – 10/10 cats

Page 13: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Discussion

Clinical and pain improvement Direct effects of UVA

Free oxygen radicals

Physical changes withinthe cornea

Biological corneal response

Page 14: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Adverse effects ?

Infections

Herpesvirus reactivation

Endothelial alterations

In humans

No adverse effects attributableto the treatment

Page 15: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Ulcerative keratitis in Horses(Dr Hellander-Edman)

9 cases Ulcerative keratitis(Dresden protocol)

8 good results (1-3 months)

1 enucleation (fungalkeratitis)

Page 16: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Worse than dogs and cats ?

Corneal /epithelial thickness

Depth of infection

Low power UVA

RF administration?

Page 17: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Protocol modifications

ConventionalProtocol

Modifications"Epi-On"

"Epi-Off"(epithelialremoval)

UV exposition3mW/cm² - 30 min.

(5,4J/cm²)

Riboflavininstillation

(30 minutes)

Low or highosmolarity RFNanostructures,adjuvants

Intrastromal injectionsIontophoresis

AcceleratedCXL9-30mW/cm²

(5,4J/cm²)

Epithelium RF distribution UVA irradiation

Page 18: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Standard or accelerated ?

Standard3 mW/cm²30 minutes

« Flash »30 mW/cm²3 minutes

5,4 J/cm²

Total durationab. 1h20

Total durationab. 40 min

Same biologicaleffects ?

Same energylevel

Page 19: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Iontophoresis

Use of a low intensity continuous electric current to enhance the penetration of a ionized substance through a biological tissue

2013Iontophoresisof RF forCXL(keratoconus)

From 1990

SteroidsAntibioticsAntifungal

AntimetabolitesOligonucleotides

DiscoveryWirz 1908

No veterinaryclinical use

(Bikbova et al.Mastropasqua et al.Touboul et al.)

No data forkeratitis

treatment

Page 20: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

IontophoresisSame therapeuticeffects (keratitis)

Page 21: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Bullous keratopathy

Endothelial alterations

Corneal edema

Bullae and epithelial ulcers

Page 22: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

« Epi-off » Stromalcompaction UVA irradiation

Hyperosmotictopical drugs

RF +Dextran 20 %

9 mW/cm²10 minutes

Bullous keratopathy

Page 23: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Results

Epithelial healing (<1 sem)

Page 24: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

ConclusionMain indication : infectious keratitis

2 main constraints- High fluence- Minimal corneal thickness

Secondary indication: Bullous keratopathy

Page 25: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose

Merci

Page 26: ESVO_SFEROV_Corneal-cross-linking_technique_and_veterinary applications_ Frank-Famose