Cross linking-iontophoresis-cats famose-ecvo_v2

EVALUATION OF ACCELERATED-CXL* AFTER

IONTOPHORESISFOR THE TREATMENT OF MELTING KERATITIS

IN 6 CATS

* Collagen Cross-Linking

Dr Frank FAMOSE – Toulouse - France

Pierre ROY – Paris - FranceLondon 2014

Melting keratitis

MMP imbalance

High perforation risk

Treatment : antibiotics& anticollagenases

Tectonic Surgery

CXL

Collagen reticulation

Anti-infectious effects

Keratocyte apoptosis

Photochemicalprocess

CXL

CXL: 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

Iontophoresis

Application of a constant electric

current to enhance penetration of a ionized substance through a tissue 2013

Iontophoresisof 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

Aim of this study

To evaluate the clinical outcome of feline melting keratitis treated by accelerated CXL

after iontophoresis of riboflavin

Inclusion criteria

Cats

Corneal melting

Poor response to

medical treatment

Inclusion criteria

Epithelial loss

Cellular infiltration andstromal dissolution

Minimal Corneal thickness

> 300 µm (OCT)

Protocol

Generalanesthesia

Cornealcleaning

Riboflavineimpregnation

ExpositionUVA 365 nm

Post-CXLtreatment

OCT

MedetomidineKetamine

Debris removalBact. sampling

PCR (FHV1)

RF 0,1% (Ricrolin TM)Iontophoresis5 min 1mA/min

30 mW/cm²3 min

5,4J/cm²

TobrexTM BID7 days

Accelerated protocol(KXLTM – Avedro)

Iontophoresisdevice

Follow-up

Inclusion D1 D4 D8 D15 D31

Pain and clinical score

Ulceration and infiltration surfaces

Follow-up

0 : absent1 : light2 : moderate3 : severe

0 : absent1 : present

Clinical score(0-18)

Pain score (0-7)

Mucopurulent discharge

Corneal edema

Corneal vascularization

Conjunctivitis

Blepharitis

Uveitis

Prostration

Aggressive behavior

Blepharospasm

Enophtalmos

Photophobia

Ocular pruritus

Defense reaction

Results Mean evolution time 40 days

Ulcer depth 21-54%

2/6 Persian

1/6 positive bacterial culture

1/6 FHV1 positive6 cats

D1 D4 D8 D15 D310

2

4

6

8

10

12

Evolution ofAverage scores

Clinical score Pain score

D1 D4 D8 D15 D310

5

10

15

20

25

30

35

Evolution of Average surfaces (mm²)

Ulcer surface Infiltration surface

Cornealvascularization

Discussion : efficacy

Reduction of clinicaland pain score

Complete Epithelial healing

Resolution of corneal melting

Comparison to conventional impregnation of RF

Distribution of RF ?

Human and rabbit studies(fluorometry, histology, HPLC, OCT…)

Clear cornea Keratitis

Anterior stroma (150 µm) :Cinstillation= 2x Ciontophoresis

Less uniform diffusion

?

Adverse effects of iontophoresis

Electric burns

Not observed in humanpatients with I < 4mA/min

High intensity current

Pain

High or low pH solutionsChemical burns

Duration of treatment ?

Instillation30 min

Iontophoresis5 min

Irradiation30 min

Accelerated CXL3-10 min

Conventional protocolDuration > 1 hour

Ionto + acc. CXL protocolDuration < 20 min.

Conclusion: IONTOPHORESIS

Results similar to conventional instillation

Resolution of corneal melting

No adverse reaction or pain

Reduction of procedure duration

Perspectives: IONTOPHORESIS

Enhanced penetration of RF…

…or other therapeutic agents

?

Thank you.