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RICROLIN TERICROLIN TE

Barcelona 06.04.’10

• Absorption and concentration of UV radiation

• Photo-sensitizing agent: production of reactive oxygen species

RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)

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• Corneal endothelium and other eye structures protection (lens and retina)

RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)

0,1% Riboflavin reduces UV intensity up to 95%.Without Riboflavin the UV absorption of almost 30% by the endothelium and 50% by the lens was measured

So, why RICROLIN TE?So, why RICROLIN TE?

Because:� It doesn’t need operating room� Corneal thickness < 400 µ� Easier technique � Pre treatment VA maintenance� Better patient compliance (children)

� No post-treatment pain� No complications derived from

disepithelization

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RiboflavinRiboflavinAbsorptionAbsorption

Epithelial barrierEpithelial barrier

Shield effectShield effect

Laser Laser intensityintensity

Dott. Stefano BaiocchiDott. Stefano Baiocchi

CORNEAL EPITHELIUMCORNEAL EPITHELIUM

1

10

100

1000

10000

100000

ribof

lavi

n (n

g/g

tissu

e)

0 5 15 *30

Exposure time(min)

Riboflavin concentration in cornea of treated patie nt

ng/g with epithelium

ng/g without

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�� BioBio--enhancerenhancer

�� FotoFoto--enhancerenhancer

Riboflavin e Dextran T500Riboflavin e Dextran T500

Trometamol (Tris -(hydroxymethyl)aminomethane) is an inert

aminoalcohol with low toxicity used to mitigate, in vitro and in

vivo, carbon dioxide and others acids, thanks to its buffer

action. It’s present in a large variety of products, i.e. cosmetics

and drugs, like buffer solution thanks to its intracellular and

extracellular alkalinizing action. Its side effects are extremely

rare; in fact, in literature, is reported only one case regarding

a periorbital dermatitis induced by a gel containing

trometamol.

So, trometamol is extremely well tolerated.

Nahas G G, Sutin K M, Fermon C et al. Guidelines for the treatment of acidaemia with THAM. Drugs 1998: 55:

191–224.

TrometamolTrometamol

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• Increase efficacy(Abdelkader H et al., AAPS PharmSciTech., 2007)

• Decrease toxicity(U.S. Pharmacopoeia, Vol. XXII)

• Improve pharmacokinetic, pharmacodynamic e biodisponibility (liposolubility)(Valles et al., Methods Find Exp Clin Pharmacol., 2006)

• Combined with EDTA allow the transit through the tight-junctions(Cover et al., Microbios, 68 1991)

TrometamolTrometamol

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CE MarkedCE Marked

Group

TreatmentObservations

MeasurementsAssessment of corneal damage

I Ricrolin

30 µl drops every 3 min for 2 h

Slit-lamp evaluation and photographs before treatment, and immediately after the last eye drop instillation; then 12, 24 and 36 h.

Methylene blue will be used as dye to assess the corneal damage.II

Ricrolin TE

0

50

100

150

200

CTR RCL

*

Den

sito

met

ry(%

of c

ontr

ol)

Quantification of corneal riboflavin TE uptake was assessed by densitometry analysis. *p<0.05 vs.CTR

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Inclusion criteriaInclusion criteria

• 20 eyes of 20 patient (14 males e 6 females)• Age included between 12 and 42 years (mean age 27 years)

• Increasing Keratoconus I and II level (Amsler –Krumeich classification)

• Treated the eye with higher corneal curvature index e lower corneal thickness

• Contralateral eye used as control• Mean corneal thickness 412,9 micron

• Controls: T0, 7 days, 15 days, 1 month, 3, 6 and 9 months

• VA tested in conditions of natural miosis with LogMar ETDRS tables

• Instruments:– biomicroscopy– ultrasounds and optic pachimetry– corneal topography and aberrometry– corneal OCT– endothelial cells counter

Materials and methodsMaterials and methods

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Height 3 mm, diameter 12 mm (external) and 10.5 (inte rnal), basal flange of 2 mm.The cilinder, introduced under the eyelid edge and directly on the cornea, works as a blepharostat, holds Ricro lin TE down, protects limbus from UV rays.

Corneal Silicon RingCorneal Silicon Ring

• RICROLIN TE 2h before the treatment (1 drop every 10 minutes)

• Anaesthetic drops preservative free• Pilocarpine 1% drops• Corneal silicon ring• RICROLIN TE 15 min before UV, then every 3-5

min during UV exposure• CBM Vega (CSO) 6 steps of 5 min each

TechniqueTechnique

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• Ophthalmic office(no operating room)

• No surgical tissue

• Corneal washing with BSS• Artificial tears (jaluronic acid and aminoacids) • Antibiotic drops preservative free

TherapyTherapy

After 2 days At the end of treatment

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ResultsResults

VisusVisus

Pre CXL 1 month 3 months 6 months 9 months

CXL Controls CXL Controls CXL Controls CXL Controls CXL Cont rols

UCVA 0,71±0.12 0,84±0.23 0,49±0.12 0,81±0.18 0,40±0.15 0,80±0.09 0,36±0.19 0,85±0.10 0,36±0.07 0,88±0.13

BCVA 0,35±0.23 0,46±0.21 0,26±0.10 0,48±0.29 0,22±0.08 0,50±0.06 0,18±0.16 0,62±0.08 0,16±0.10 0.66±0.11

p<0.05

PachimetryPachimetryCXL

Pre: 412,9±21.5Post: 410,3 ±15.3

ControlsPre: 423,3±12.2Post: 409,0 ±16.5

data not statistically significants (p<0.05)

ResultsResults

Pre CXL 1 month 3 months 6 months 9 months

CXL Controls CXL Controls CXL Controls CXL Controls CXL Cont rols

Sim kS

51,02±1.10 51,12±1.02 49,05±0.92 51,10±1.04 48,65±0,89 51,42±0,96 47,82±0,78 51,40±0,92 47,85±0,71 51,32±1.13

Sim kF

45,13±0.97 46,12±0.99 44,46±1.03 46,12±0.65 44,13±0.89 46,52±0.91 44,57±1,11 46,74±0.71 47,85±0.84 46,23±0.50

Sim Cyl

5,89 4,91 4,59 4,98 4,55 4,91 3,32 4,70 3,55 5,12

p<0.05

Central keratometry (3 mm)Central keratometry (3 mm)

endothelial cells counter (cell/mmendothelial cells counter (cell/mm 22))CXL

Pre: 2427 ± 236.4Post: 2387 ± 361.0

ControlsPre: 2523 ± 198.2Post: 2474 ± 241.0

data not statistically significants (p<0.05)

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Pre CXL 1 month 3 months 6 months 9 months

CXL Controls CXL Controls CXL Controls CXL Controls CXL Cont rols

Kcak

59,12±1.10 58,89±2.02 58,01±0.92 58.92±2.34 57,42±0,89 59,43±1.87 57,31±0,78 59,86±2.45 57,56±1.21 60,06±1.13

Mc

56,46±0.97 56,31±1.93 55,73±1.41 56,29±2.18 55,52±0.89 57,02±0.91 55,49±1,11 57,59±2.02 55,51±1.23 58,18±0.93

Ma

23,89±0.75 21,91±2.05 20,07±2.42 21,98±1.67* 20,09±2.50 23,06±1.4 20,01±2.02 23,21±0.67 20,12±1.22 23,81±0.88

Maximal curvature (KcAK) Maximal curvature (KcAK) and CLMI indexes (Ma, Mc)and CLMI indexes (Ma, Mc)

ResultsResults

p<0.05 *p>0.05

Pre CXL 1 month 3 months 6 months 9 months

CXL Controls CXL Controls CXL Controls CXL Controls CXL Cont rols

Rms4,68±0.27 4,43±0.75 4,21±0.66 4,12±0.83 3,75±0,59 4,39±1.47 3,01±0,38 4,56±2.45 3,21±0.45 4,71±1.02

Coma

2,21±0.97 2,28±1.93 2,19±1.04 2,10±1.74 1,72±0.32 2,23±1.05 1,65±1,01 2,41±1.88 1,59±1.23 2,39±0.93

S.A.0,98±0.15 1,12±.052 0.77±0.42 1,08±0.67 0,45±0.59 1,26±0.72 0,45±0.39 1,26±0.47 0,35±0.64 1,31±0.98

p<0.05

ResultsResults

Corneal aberrometryCorneal aberrometry

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ResultsResults

corneal OCTcorneal OCT

1 month

Take home messageTake home message•• Better compliance of the patientBetter compliance of the patient (possibility to treat (possibility to treat

patients under 15 years old and ”complicated subject s”)patients under 15 years old and ”complicated subject s”)•• No postNo post--treatment paintreatment pain•• Corneal thickness < 380 micronCorneal thickness < 380 micron•• Pre treatment VA maintenancePre treatment VA maintenance•• Adjuvant treatment of “traditional CXL” Adjuvant treatment of “traditional CXL” (one technique (one technique

has the opportunity to reinforce the effectiveness of the has the opportunity to reinforce the effectiveness of the other)other)

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•• The The trans epithelial CXLtrans epithelial CXL treatment doesn’t need treatment doesn’t need operating roomoperating room

•• Corneal Silicon RingCorneal Silicon Ring works as a works as a blepharostatblepharostat , , increase the increase the contact timecontact time between Ricrolin TE between Ricrolin TE and corneal epithelium, and corneal epithelium, protects limbus and stem protects limbus and stem cellscells from UV raysfrom UV rays

Take home messageTake home message