cxl te istanbul 2011
TRANSCRIPT
REFRACTIVE,TOPO-ABERROMETRICAL
and CORNEAL BIOMECHANICAL CHANGES AFTER TRANSEPTHELIAL CROSSLINKING (TE-CXL):
17 MONTHS OF FOLLOW-UP
Luca Gualdi D.O.M.A. srl Rome (Italy)www.gualdi.it [email protected]
Istanbul (Turkey) January 19th, 2011
CORNEAL CROSSLINKING with Riboflavin 0.1% (Vit B2) increase corneal rigidity by 328,9%
Increased rigidity of the cornea caused by intrastromal cross-linking” Ophthalmologe. 1997 Dec;94(12):902-6 Spörl E, Huhle M, Kasper M, Seiler T.
CONVENTIONAL CXL “SIDE EFFECTS”
- Post-operative pain- Post-operative “foggy vision”- Prolonged theraphy (expecially corticoides)
- Risk of infection (due to the epithelial debridment)
How to riduce these side effects ???
...through the corneal epithelium...
• • RIBOFLAVIN (Vit B2) =376 Dalton HYDRO-SOLUBLE MOLECULE •
Corneal cross-linking in vivo and ex vivo Riboflavin concentration determined by HPCL chromatography in corneal stroma exposed with and without epithelium (Caporossi A. et al. J Cataract Refract Surg. 2009 May;35(5):893-9.)
“Biomechanical and histological changes after corneal crosslinking with and without epithelial debridment” (Wollensak G. et al. J Cataract & Refract Surg 2009, 35.540-546)
CORNEAL EPITHELIUM = LYPO-SOLUBLE BARRIER can accept only lypo-soluble molecules smaller than about 500 Dalton
RIBOFLAVIN cannot pass beyond the CORNEAL EPITHELIUM
Role of benzalkonium chloride (BAK) on corneal epithelium
Corneal epithelium tight junctions are the most important barrier for Riboflavin permeability
BAK (=contained in many eye drop concentrations 0.0075%-0.02) loosens epithelial tight junctions and enhances permeability for pharmaceutical agents
MC Carey B. In vivo corneal epithelial permeability following treatment with prostaglandin analogs with or without benzalkonium chloride J. Ocul Pharmacol Ther 2007;23:445-451
Cha SH, lee JS,Oum BS, Kim CD, Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Experiment Ophthalmol 2004,32: 180-184
Burstein NL. Preservative alteration of corneal permeability in humans and rabbits. Invest Ophthalmol Vis Sci 1984;25:1453-1457
Rabbit corneal epithelium treated with a product preserved with sodium perborate q.i.d. for 7 days. The tissue reveals a mostly normal epithelium with extensive microvilli and tight epithelial cell to cell junctions (32,000X).
Rabbit corneal epithelium treated with a product preserved with 0.001% polyquaternium-1 q.i.d. for 7 days. The tissue reveals extensive superficial epithelial erosion and lack of protruding microvilli (32,000X).
Role of benzalkonium chloride (BAK) on corneal epithelium
CXL with BAK suggested by Pinelli and Boxer Walcher success only by stable visual acuity and corneal topographies
Pinelli R. Corneal Cross-linking with riboflavin:enteriging a new era in ophthalmology. Ophthalmology Times Europe 2006:2-36-38
Pinelli R. Mometto C. Corneal abrasion for CCL contra. 3rd internatonal congress of corneal cross linking. Zurich, 7-8 Dec 2007
Boxer Wachler B. Corneal collagen crosslinking with riboflavin. Cataract & Refractive Surg Today. 2006, 1:73-74
RICROLIN TE® = Hypotonic ophthalmic solution containing Riboflavin o.1% and enhancers helping the Riboflavin pass through the intact corneal epithelium
TRANSEPITELIAL CROSS-LINKING
Trometamol Amino-alcohol which improves the pharmacodynamics
and bioavability of Riboflavin and increases its passage
into the corneal stroma. Sodic ETDA Helps to break cell-cell bonds,to facilitate the penetration
of Riboflavin.
RICROLIN TE ® 0373 = Riboflavin 0,1% + Enhancers
Enhancers
PARACELLULAR ROUTE (predominantly HYDROPHILIC DRUGS)
INTRACELLULAR ROUTE (predominantly LIPOPHILIC DRUGS)
The “Enhancers” increase ocular penetration of hydrophilic drugs by transiently relaxing EPITHELIAL TIGHT JUNCTIONS, temporarily opening a paracellular route for drug adsorption
INTRACELL
ULAR
PARACELLULAR
Corneal epithelium
CORNEAL EPITHELIUM 30 min. after CXL TE
With courtesy of Dr. Cosimo Mazzotta
RIBOFLAVIN 0,1% TE (TRANSEPITELIAL) PENETRATION INTO THE ANTERIOR STROMA (89-99 microns by PENTACAM)
“ANTERIOR CROSS-LINKING”
No keratocytes apoptosis Less biomechanical effect?
Courtesy of F. Hafezi
THE EPITHELIAL MAP
The earliest abnormalities of keratoconus occur in the epithelial basement membrane and Bowman's layer. The basement membrane may be disrupted (arrow 6) and duplicated. Bowman's layer (arrow 3) is disrupted (arrow 4) and fibrous tissue is interposed between the epithelial basement membrane and Bowman' layer (arrows 5). There is also
stromal scarring.
ARTEMIS Digital Ultrasound®
Corneal epithelial thickness profile in the diagnosis of keratoconusDan Z. Reinstein – Journal of Refractive Surgry Vol. 25, July 2009
EPITHELIAL MAPEpithelial doughnut pattern characterized by epithelial thinningsourronded by anulus of thicker epithelium coincident with an eccentricposterior elevation BSS apex, is consistent with KERATOCONUS
EPITEHELIAL THINNING
EPITHELIAL THICKENING
EPITHELIAL THICKNESS MAP
TOPOGRAPHY MAP
NORMAL EYE KERATOCONUS EYE
STEEPEST POINT =THICKEST POINT
STEEPEST POINT = THINNEST POINT
RIBOFLAVIN MAY PENETRATE EASIER WHERE THE EPITHELIUM IS THINNER (with better effect on the apex of the cone)
PERSONAL EXPERIENCE with CXL TE
PRE-POST OP: BUVA/BCVA Topography (CSO®,OPD-scan ®), Tomography (PENTACAM ®, VISANTE ®), Corneal histeresis and corneal resistence factor (Ocular Response Analyzer ®), Corneal endotelial count (CSO ®), Confocal microscopy (CONFOSCAN ®), Aberrometry (CSO ®, OPD-scan ®)
MATHERIALS: 48 eyes (20 with follow-up > 1 year) OXIBUPROCAINE (0,02 % BENZALCHONIUM CLORIDE)
VEGA CROSS-LINKER ® RICROLIN TE ®
METHODS: 1HOUR pre-instillation of oxibuprocaine (0,02 % benzalchonium cloride) and RICROLIN TE® >10 min. with the patient in supine position before UVA irradiation with the anulus, 30 min. IRRADIATION TIME (9mm diameter): UVA 370 nm at 3.0 mW/cm2 (dose:% 5.4 J/cm2)
2 RICROLIN TE ® DROPS EVERY 2.5 MINUTES
PERSONAL EXPERIENCE
CONVENTIONAL CXL TRANSEPITELIAL CXL (TE)
NUMBER OF CASES 64 eyes (from May 2007 to today) 48 eyes (from september 2009 to today)
FOLLOW-UP 43 months 17 months
GAINED LINES OF BUVA 0,9 0,7
GAINED LINES OF BCVA 0,6 0,2
LOST LINES OF BUVA and BCVA 0 0
STEEPEST K AVERAGE DECREASE -1,74 D -1,04 D
MEAN RMS ERROR DECREASE -1,27 -0,77
DISCOMFORT EVALUATION (0-5) 4 0,5
CORNEAL HISTERESIS (CH) No statistical significant difference (range -0.4 mmHg/ +0.5 mmHg)
No statistical significant difference (range -0.4 mm Hg / +0.6 Mm Hg)
CORNEAL RESISTENT FACTOR (CRF) No statistical significant difference (range -0.4v mmHg/ -0.5 mm Hg)
No statistical significant difference (range -0.5 mmHg/ +0.5 mm Hg)
“DEMARCATION LINE” 170 to 380 micron 50 to 150 micron
ENDOTHELIAL CELL LOSS None None
MEAN TOPOGRAPHIC INDEX (EYETOP®/CSO)
44,80
45,00
45,20
45,40
45,60
45,80
46,00
46,20
CSO EYE TOP:Mean SIMK imrovement pre-post surgery
Simk pre Simk post
CSO EYE TOP:Mean AK improvement pre-postsurgery
54,42
54,27
54,15
54,20
54,25
54,30
54,35
54,40
54,45
AK pre
Ak post
CSO EYE TOP:Mean SAI imrovement pre-post surgery
4,21
3,95
3,80
3,85
3,90
3,95
4,00
4,05
4,10
4,15
4,20
4,25
Sai preop
Sai postop
1,382666667
1,209796296
CSO EYE TOP:Mean COMA improvement pre-postsurgery
COMA pre
COMA post
-2,28
-1,92
-2,40
-2,30
-2,20
-2,10
-2,00
-1,90
-1,80
-1,70
1
CSO EYE TOP:Mean LSA pre-postsurgery
LSA pre
LSA post
1,95
1,65
0,56 0,51
0,00
0,50
1,00
1,50
2,00
2,50
NIDEK OPD Scan II:Mean SAI and IAI pre-postsurgery
SAI pre
SAI post
IAI pre
IAI post
NIDEK OPS Scan II: Mean SIMK1, SIMK2 e MINK improvement pre-postsurgery
48,5747,97
44,57 44,14
42,6441,83
38,00
40,00
42,00
44,00
46,00
48,00
50,00
SIMK1 pre
SIMK1 post
SIMK2 pre
SIMK2 post
MINK pre
MINK post
MEAN KLYCE’S INDEX CHANGES (OPD-Scan II ®)
70,8067,83
55,9851,62
0,00
10,00
20,00
30,00
40,00
50,00
60,00
70,00
80,00
NIDEK OPD Scan II:Mean % AA and D CVP improvement pre-postsurgery
AA pre
AA post
CVP pre
CVP post
NIDEK OPD Scan II:Mean SRI and SRC pre-postsurgery
1,02
0,93
1,08
1,03
0,85
0,90
0,95
1,00
1,05
1,10
SRI pre
SRI post
SRC pre
SRC post
NIDEK OPD Scan II:Mean CEI improvement pre-postsurgery
0,79
0,52
0,00
0,10
0,20
0,30
0,40
0,50
0,60
0,70
0,80
0,90
CEI pre
CEI post
NIDEK OPD Scan II:Mean CYL pre-postsurgery
3,90
3,49
3,20
3,30
3,40
3,50
3,60
3,70
3,80
3,90
4,00
1
CYL pre
CYL post
NIDEK OPD Scan II:Mean COMA improvement pre-postsurgery
1,13
0,90
0,00
0,20
0,40
0,60
0,80
1,00
1,20
COMA pre
COMA post
NIDEK OPD Scan II:Mean LSA improvement pre-postsurgery
-0,17
-0,08
-0,18
-0,16
-0,14
-0,12
-0,10
-0,08
-0,06
-0,04
-0,02
0,00
LSA pre
LSA post
MEAN ABERROMETRIC CHANGES (OPD-Scan II® / Nidek)
OCULUS PENTACAM:Mean IHA improvement pre-postsurgery
17,85
13,72
0,00
2,00
4,00
6,00
8,00
10,00
12,00
14,00
16,00
18,00
20,00
IHA pre
IHA post
OCULUS PENTACAM:Mean CKI improvement pre-post surgery
1,023
1,016
1,012
1,014
1,016
1,018
1,020
1,022
1,024
CKI pre
CKI post
OCULUS PENTACAM:Mean IVA improvement prepsurgery
0,67
0,60
0,56
0,58
0,60
0,62
0,64
0,66
0,68
IVA pre
IVA post
MEAN TOMOGRAPHIC AMBROSIO’S INDEX (Pentacam / Oculus ®)
THINNEST POINT (Pentacam / Oculus)®
400.00
410.00
420.00
430.00
440.00
450.00
460.00
470.00
480.00
490.00
500.00
478.53
487.53
OCULUS PENTACAM: Mean Thinnest point change pre-postsurgery
Thinnest point pre
Thinnest point post
NO SIGNIFICANT CHANGE= +9 micron (range -11/ +15 micron)
OCULAR RESPONSE ANALYSER (Reichert®)
Mean CH pre-op=9,2 mmHg Mean CRF pre-op=9,7 mmHg
PRE-OP POST-OP
Mean CH post-op= +0,1mmHg (range=-0,4/+0,5 mmHg)
Mean CRF post-op= +0,2mm Hg (range=-0,4/ +0,7 mmHg)
NO SIGNIFICANT CHANGE ON PEAKS, CH AND CRF
CORNEAL ENDOTHELIUM
PRE-OP POST-OP
NO SIGNIFICANT CHANGE IN POLIMEGATHISM, PLEIOMORFISM AND n.CELLS
QUANTITY OF VISION
Mean UCVA improvement= +0,73 lines (range -0,5/+2)Mean BCVA improvement= +0,21 lines (range -0,5/+1)
UCVA and BCVA average improvement pre vs post surgery
0,73
0,21
-1
-0,8
-0,6
-0,4
-0,2
0
0,2
0,4
0,6
0,8
1
Mean Average UCVAimprovement
Mean average BCVAimprovement
PRE-OP POST-OP
QUALITY OF VISION
“SPECIAL CASES”
PELLUCIDA MARGINAL DEGENERATION
PRE-OP
POST-OP
TRISOMY 21 PATIENT
FRUST KERATOCONUS
PRE-OP POST-OP
PEDIATRIC PATIENT
CORNEAL ECTASIA
TRANSEPITELIAL CROSS-LINKING (CXL TE)
PRO= - Allowed treatments also for corneal thickness < 400 micron - No post-operative pain - No visual worsening due to corneal opacity (expecially in the 1° month)
- No discomfort - Rapid visual recovery - No complications or risk of infection due to epithelium removal - No long term theraphy (expecially for corticoids)
- No necessairly need to be performed in the surgery theatre - Easier bilateral procedure - Less costs (no surgery theatre,no massive and prolonged therapy less post-operative consultants, no LAC, etc.)
CONTRA= - Less Riboflavin penetration into the posterior stroma
CONCLUSIONS
TRANSEPITHELIAL CXL with RICROLIN TE ® is an effective way to stop or reduce ectasic disease such as: keratoconus, PMD and post-lasik ectasia.
The penetration of RICROLIN TE® into the anterior stroma was confirmed by many diagnostic instruments (VISANTE®,PENTACAM®, CONFOSCAN®).
The effects were confirmed from pre-op to post-op BUVA, BAVC and by topo-aberrometrical stability or decreasing of the apex of the cone (CSO®, OPD®, PENTACAM®).
Anyway the amount of RICROLIN TE® doesn’t reach the posterior stroma and this could lead to less stiffening effect.
RIBOFLAVIN 0,1% TE (TRANSEPITELIAL) PENETRATION INTO THE ANTERIOR STROMA (about 150 microns)
CONVENTIONAL RIBOFLAVIN 0,1% PENETRATION INTO THE ANTERIOR AND POSTERIOR STROMA (about 380 microns)
WHICH CROSS-LINKING?CONVENTIONAL CXL or TRANSEPIELIAL CXL
CONCLUSIONS
To have a deeper penetration also in the posterior stroma, further studies and longer follow-up will help to modify: - Fluence of UVA irradiation - Time of exposion - Wavelight
CONVENTIONAL AND TRANSEPITHELIAL CXL TODAY MUST COHESIST (The ophthalmologist have to address the patient to the best way because each case, each person, each ectasic disorder, is different).
THANK YOU [email protected]