“post-operative follow-up” - a.i.che. associazione … of l’aquila surgical department eye...

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University of L’Aquila Surgical Department Eye Clinic Head: Prof. Leopoldo Spadea University of L’Aquila Surgical Department Eye Clinic Head: Prof. Leopoldo Spadea L. Spadea, B.M. Saviano, A. Fiasca, A. Di Gregorio L. Spadea, B.M. Saviano, A. Fiasca, A. Di Gregorio Siena X LINKING Siena X LINKING Siena, February, 2 nd 2007 Siena, February, 2 nd 2007 “Post-Operative Follow-up” “Post-Operative Follow-up” Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

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University of L’Aquila

Surgical Department

Eye Clinic

Head: Prof. Leopoldo Spadea

University of L’Aquila

Surgical Department

Eye Clinic

Head: Prof. Leopoldo Spadea

L. Spadea, B.M. Saviano,

A. Fiasca, A. Di Gregorio

L. Spadea, B.M. Saviano,

A. Fiasca, A. Di Gregorio

Siena X LINKING Siena X LINKING

Siena, February, 2nd 2007 Siena, February, 2nd 2007

“Post-Operative Follow-up” “Post-Operative Follow-up”

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

X LINKING

Therapeutic management

�PRE-SURGERY

• ORAL SUPPLEMENTATION OF AMINO ACIDS

Since 5 days before surgery

GLYCINA

1.5g/day

L-PROLYNA

1.75g/day

L-LYSINA

0.25g/day

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

X LINKING

Therapeutic management

�Ist week post-surgery

(glycina, L-prol,L-lys) ×1 •Amino acids Oral solution

(hyaluronic acid 0.3%)

×6

•Tear substitute Preservative-free eye drops

(indomethacin 0.1%) × 3 •Anti-inflammatory N.S. Preservative-free eye drops

(netilmycin 0.3%) ×3

•Antibiotic Preservative-free eye drops

× 6 days Therapeutic CL

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

�2nd week post-surgery (only with a complete re-epithelialization)

X LINKING

Therapeutic management

(hyaluronic acid 0.3%) ×6 •Tear substitute Preservative-free eye drops

(indomethacin 0.1%) × 3 •Anti-inflammatory N.S. Preservative-free eye drops

(fluorometh. ac. 0.1%) ×3 •Corticosteroid Preservative-free eye drops

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

� 3rd week post-surgery

(hyaluronic acid 0.3%) ×6 •Tear substitute Preservative-free eye drops

(fluorometh. ac. 0.1%) ×2 •Corticosteroid Preservative-free eye drops

X LINKING

Therapeutic management

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

� 4th week post-surgery

(hyaluronic acid 0.3%) ×6 •Tear substitute Preservative-free eye drops

(fluorometh. ac. 0.1%) ×1 •Corticosteroid Preservative-free eye drops

X LINKING

Therapeutic management

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Why we used Amino Acids? they are very important for the cell life

�Epithelial cell differentiation

�Epithelial healing

�Energy producing

�Tear and serum concentrations = 4:1

Re-epithelialization is possible

and qualitatively optimal

X LINKING

Therapeutic management

(Zieske JD, 1986;

Flachmeyer, 1963)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

High concentration of Amino Acids in

serum and tear (in vivo and in vitro)

improves corneal re-epithelialization

(Vinciguerra P. JRS 2002; Rivaud C. J Fr Ophthalmol 1987)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

�There is an extensive interaction between the

surface epithelial cells and the stromal

keratocytes regulated by molecular signs,

cytokines and growth factors. The corneal

repair system is not perfect and collagen

opaque can be produced.

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Molecular regulation of epithelial cells and keratocytes

in corneal wound healing

Molecular regulation of epithelial cells and keratocytes

in corneal wound healing

Epithelial damage Epithelial damage

IL-1 IL-1 Fas-L Fas-L

Apoptosis of keratocytes Apoptosis of keratocytes

PDGF PDGF

Migration and

proliferation of

keratocytes

Migration and

proliferation of

keratocytes

Transformation and

persistence of myofibroblast

Transformation and

persistence of myofibroblast TGF-β TGF-β

Epithelial

healing

Epithelial

healing EGF, TGF-α, HGF,

KGF

EGF, TGF-α, HGF,

KGF

Wilson, 1996 - Mohan, 1997 - Kim, 1999 - Jester, 1999 - Schultz 1994 - Wilson 1999 Wilson, 1996 - Mohan, 1997 - Kim, 1999 - Jester, 1999 - Schultz 1994 - Wilson 1999

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Why we used topical steroids? �Regulation of proliferation and migration of

keratocytes

�Regulation of transformation

keratocytes/activated fibroblasts

�Regulation of fibroblastic activity

Prevention and treatment of

corneal opacities

X LINKING

Therapeutic management

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

� Keratoconic corneas are anatomically and

functionally modified

(Chi HH. Am J Ophthalmol 1956)

Epithelium

•Thinning irregular

•Basal epithelial degenerated cells

•Basal membrane destruction

Bowman’s Membrane

•Fibrillar degeneration

•Fragmentation and progressive

destruction

Stroma

•Reduction of lamellae

•Collagen production

•Amiloid deposition

•Keratocytes in various stages of

differentiation

Epithelium

•Thinning irregular

•Basal epithelial degenerated cells

•Basal membrane destruction

Bowman’s Membrane

•Fibrillar degeneration

•Fragmentation and progressive

destruction

Stroma

•Reduction of lamellae

•Collagen production

•Amiloid deposition

•Keratocytes in various stages of

differentiation

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

�Rabbit eyes that

underwent to combined

riboflavin/UVA treatment

showed apoptosis of

keratocytes down to a

depth of 50µm in the

anterior stroma

(Cho KS. IOVS, 1999)

�Riboflavin by itself is not cytotoxic, but as

photosensitizer, it increases the absorption of UVA,

which induces the cellular damage

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

� Combined riboflavin/UVA

treatment showed a dose

dependent damage of stromal

keratocytes

� Cytotoxic irradiance

threshold (Lambert-Beer low)

0.49-0.77 mW/cm2 = 0.8-1.3

J/cm2

(Wollensak G. Cornea, 2004)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

RESULTS

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

7 days 14 days 21 days 28 days

Absent

Light

Moderate

Severe

Epithelial Defects Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Conjunctival Hyperemia

0

10

20

30

40

50

60

70

80

90

100

7 days 14 days 21 days 28 days

Absent

Light

Moderate

Severe

steroids

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

0

10

20

30

40

50

60

70

80

90

100

7 days 14 days 21 days 28 days

Absent

Light

Moderate

Severe

Subjective Discomfort steroid

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Reduction of the

proteolytic

activity in

trabecular cells

Deposition of

components of extra

cellular matrix

Increase of

resistance

Steroids and IOP

The increase of IOP is reversible (Shaikh S. JCRS 2002)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

1212

1414

1515

1616

1313

1111

Intraocular Intraocular

Pressure Pressure

15.28

14.50

14.76

14.23

mm

Hg

mm

Hg

RESULTS

Preop. (26 pz)

1 Month (26 pz)

3 Months (26 pz)

6 Months (21 pz)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)

Documentazione distribuita da A.I.CHE. - Associazione Italiana CHEratoconici ONLUS (www.assocheratocono.org)