Post on 12-Mar-2018
ASCRS diams ASOA Symposium amp Congress
Technicians amp Nurses Program
May 6-10 2016 ndash New Orleans
462016
1
CORNEAL CROSSLINKING
BACKGROUND TECHNIQUES RESULTS JCAHPO
NEW ORLEANS 2016 James J Salz MD
Laser Vision Medical Group
Los Angeles CA
Clinical ProfessorOphthalmology
University of Southern California
(corneal cross linking is not FDA approved in US)
(many slides courtesy of Yaron Rabinowitz M D) ldquoHOT TOPICrdquo
MANY PUBLICATIONS
NOW IN THE LITERATURE UNDER FDA STUDY AT
SEVERAL CENTERS IN US
Cornea Genetic Institute near
Cedars-Sinai Hospital in Los Angeles PI Dr Yaron
Rabinowitz
2 basic techniques being
investigated
Classic- epithelium removed
ldquoEpi onrdquo epithelium not
removed
KERATOCONUS INCIDENCE 12000 PATIENTS IN U S
KERATOCONUS- BULGING
AND THINNING OF CORNEA USUALLY
INFERIORLY DUE TO WEAKENED CORNEAL COLLAGEN LAMELLAE
SIDE VIEW OF
KERATOCONUS
BACKGROUND
What is Crosslinking
1 Process well known in material sciences
2 The addition of molecular bonds to increase
the mechanical strength of tissue
3 An enzymatic process
bull Cross-links can be induced enzymatically by
means of aldehydes chemical fixatives and by
photosensitizing radiation
1) Photosensitizer 2) Chemicals 3) Aldehyde
+ light Fixatives Sugars
ie riboflavin + UV ie glutaraldehyde ie glucose
J Refract Surg 1999 15 711-713
Induction of cross-links in corneal tissue Spoerl E Huhle M Seiler T
Exp Eye Res 1998 Jan66(1)97-103
THEO SEILER M D
SWITZERLAND
FIRST TO PROPOSE COLLAGEN CROSS-
LINKING TO SLOW PROGRESSION OF
KERATOCONUS IN 1998
YARON RABINOWITZ MD
LOS ANGELES CA
Dr Rabinowitz first classified keratoconus by patterns on
topography
462016
2
in vivo-experiments reveal UV-radiation and riboflavin to be the most effective and the least harmful procedure
Photo+Light Fixitive Sugars
1 Riboflavin (vit B2) + Ultraviolet radiation
2 Production of oxygen radicals
O2-
3 Induction of collagen cross-links -CH2-CH2-CH2-CH = NH-CH2-CH2-CH2-CH2-
collagen fibril collagen fibril
Basics in Crosslinking
Crosslinking
STEPS IN CROSSLINKING (CXL) Calibrate laser
Anesthesia- proparacaine 05
Debride central 7 mm epithelium
Use freshly prepared riboflavin solution (01)(10mg riboflavin-5-phosphate in 10 ml dextran 20 )
Apply every 2 minutes for 30 minutes prior to procedure
Check for Flare in AC
UV radiance of of 3mWcm2
and a wavelength of 370nm ndash 5 cm from eye homogenous
Cornea must be a least 400um
TECHNIQUE
APPLICATION OF RIBOFLAVIN
1 DROP Q 2 MINUTES FOR X 15
RIBOFLAVIN DIFFUSES INTO CORNEAL STROMA
UV RADIATION
U V LIGHT SYSTEM APPEARANCE OF CORNEA DURING UV LIGHT APPLICATION
LABORATORY STUDIES 2003- PRESENT
Biomechanical
Biochemical
Thermal
Morphological
Effect on keratocytes endothelium
462016
3
Crosslinking Extensiometry
RESEARCH - Extensiometry In-Vitro Testing of Corneal Stiffness
Sept 2003
Human Cornea
Porcine Cornea
rarr3289 increase of
rigidity in human cornea
LONG-TERM BIOMECHANICAL PROPERTIES OF RABBIT CORNEA AFTER PHOTODYNAMIC COLLAGEN CROSSLINKING
WOLLENSAK G IOMDINA E ACTA OPHTHALMOL 2008 JUN 11
In the treated rabbit cornea a decrease in
ultimate strain (of 057-784) were found over a
time period of up to 8 months after crosslinking treatment
RiboflavinUVA-induced collagen crosslinking
leads to a long term increase in biomechanical
rigidity which remains stable over time
COLLAGEN FIBER DIAMETER IN RABBIT CORNEAS WOLLENSAK G WILSCH M SPOERL E SEILER T
CORNEA 2004 JUL23(5)503-7
Cross linking using riboflavinUVA leads to a significant increase in corneal collagen diameter
Morphologic correlate of the cross linking process leading to an increase in biomechanical stability
Courtesy
Prof Wollensak
anterior effect
Increase by 12 in fiber diameter
Courtesy Prof Wollensak
CYTOTOXICITY OF CROSS-LINKING (CXL)
Rabbits irradiated with UVA 370 um
Cornea 2004 2343-49
RiboflavinUVA treatment leads to a dose-dependent
keratocyte damage that can be expected in human corneas
down to a depth of 300u repopulation occurs at 6 months
462016
4
CORNEAL ENDOTHELIAL CYTOTOXICITY OF RIBOFLAVINUVA TREATMENT IN VITRO WOLLENSAK G SPOumlRL E REBER F PILLUNAT L FUNKR
OPHTHALMICRES 2003 NOV-DEC35(6)324-8
A cytotoxic effect on endothelial cells was demonstrated at a
thickness of lt 400um
Patients whose corneas are less than 400um should be excluded for treatment
Endothelial cell culture
YOPRO-stain
Courtesy Prof Wollensak
SLITLAMP APPEARANCE
Early mild diffuse Haze that dissipates with time
Likely due to the linking amp spacing of fibers
6 weeks after corneal collagen
cross-linking reveals bundles
of highly reflective striae
SAFETY OF UVA-RIBOFLAVIN CROSS-LINKING OF THE
CORNEA SPOERL E MROCHEN M SLINEY D TROKEL S SEILER T
CORNEA 2007 MAY26(4)385-9 REVIEW ARTICLE
The currently used UVA radiant exposure of 54 mJcm and the corresponding irradiance of 3 mWcm2 is below the known damage thresholds of UVA for the corneal endothelium lens and retina
CLINICAL STUDIES MAY 2003
22 patients ndash 2 to 4 yrs
no progression in all eyes
Improved in VA in 1522
flattening of Max K by 2D in 1622
eyes
CHANGE OF MAXIMAL K-VALUE
CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-LIGHT IN
KERATOCONUS LONG-TERM RESULTS RAISKUP-WOLF ET AL 2008
J CATARACT REFRACT SURG 2008 796-801) DRESDEN 7-YEARS-RESULTS
Decrease of keratectasia year 1= 27D year 2 = 22D year 3 = 48D
Visual acuity improved by 1 line per year in 54 in first three years
2 patients had continued progression and were x-linked a 2nd time
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
1
CORNEAL CROSSLINKING
BACKGROUND TECHNIQUES RESULTS JCAHPO
NEW ORLEANS 2016 James J Salz MD
Laser Vision Medical Group
Los Angeles CA
Clinical ProfessorOphthalmology
University of Southern California
(corneal cross linking is not FDA approved in US)
(many slides courtesy of Yaron Rabinowitz M D) ldquoHOT TOPICrdquo
MANY PUBLICATIONS
NOW IN THE LITERATURE UNDER FDA STUDY AT
SEVERAL CENTERS IN US
Cornea Genetic Institute near
Cedars-Sinai Hospital in Los Angeles PI Dr Yaron
Rabinowitz
2 basic techniques being
investigated
Classic- epithelium removed
ldquoEpi onrdquo epithelium not
removed
KERATOCONUS INCIDENCE 12000 PATIENTS IN U S
KERATOCONUS- BULGING
AND THINNING OF CORNEA USUALLY
INFERIORLY DUE TO WEAKENED CORNEAL COLLAGEN LAMELLAE
SIDE VIEW OF
KERATOCONUS
BACKGROUND
What is Crosslinking
1 Process well known in material sciences
2 The addition of molecular bonds to increase
the mechanical strength of tissue
3 An enzymatic process
bull Cross-links can be induced enzymatically by
means of aldehydes chemical fixatives and by
photosensitizing radiation
1) Photosensitizer 2) Chemicals 3) Aldehyde
+ light Fixatives Sugars
ie riboflavin + UV ie glutaraldehyde ie glucose
J Refract Surg 1999 15 711-713
Induction of cross-links in corneal tissue Spoerl E Huhle M Seiler T
Exp Eye Res 1998 Jan66(1)97-103
THEO SEILER M D
SWITZERLAND
FIRST TO PROPOSE COLLAGEN CROSS-
LINKING TO SLOW PROGRESSION OF
KERATOCONUS IN 1998
YARON RABINOWITZ MD
LOS ANGELES CA
Dr Rabinowitz first classified keratoconus by patterns on
topography
462016
2
in vivo-experiments reveal UV-radiation and riboflavin to be the most effective and the least harmful procedure
Photo+Light Fixitive Sugars
1 Riboflavin (vit B2) + Ultraviolet radiation
2 Production of oxygen radicals
O2-
3 Induction of collagen cross-links -CH2-CH2-CH2-CH = NH-CH2-CH2-CH2-CH2-
collagen fibril collagen fibril
Basics in Crosslinking
Crosslinking
STEPS IN CROSSLINKING (CXL) Calibrate laser
Anesthesia- proparacaine 05
Debride central 7 mm epithelium
Use freshly prepared riboflavin solution (01)(10mg riboflavin-5-phosphate in 10 ml dextran 20 )
Apply every 2 minutes for 30 minutes prior to procedure
Check for Flare in AC
UV radiance of of 3mWcm2
and a wavelength of 370nm ndash 5 cm from eye homogenous
Cornea must be a least 400um
TECHNIQUE
APPLICATION OF RIBOFLAVIN
1 DROP Q 2 MINUTES FOR X 15
RIBOFLAVIN DIFFUSES INTO CORNEAL STROMA
UV RADIATION
U V LIGHT SYSTEM APPEARANCE OF CORNEA DURING UV LIGHT APPLICATION
LABORATORY STUDIES 2003- PRESENT
Biomechanical
Biochemical
Thermal
Morphological
Effect on keratocytes endothelium
462016
3
Crosslinking Extensiometry
RESEARCH - Extensiometry In-Vitro Testing of Corneal Stiffness
Sept 2003
Human Cornea
Porcine Cornea
rarr3289 increase of
rigidity in human cornea
LONG-TERM BIOMECHANICAL PROPERTIES OF RABBIT CORNEA AFTER PHOTODYNAMIC COLLAGEN CROSSLINKING
WOLLENSAK G IOMDINA E ACTA OPHTHALMOL 2008 JUN 11
In the treated rabbit cornea a decrease in
ultimate strain (of 057-784) were found over a
time period of up to 8 months after crosslinking treatment
RiboflavinUVA-induced collagen crosslinking
leads to a long term increase in biomechanical
rigidity which remains stable over time
COLLAGEN FIBER DIAMETER IN RABBIT CORNEAS WOLLENSAK G WILSCH M SPOERL E SEILER T
CORNEA 2004 JUL23(5)503-7
Cross linking using riboflavinUVA leads to a significant increase in corneal collagen diameter
Morphologic correlate of the cross linking process leading to an increase in biomechanical stability
Courtesy
Prof Wollensak
anterior effect
Increase by 12 in fiber diameter
Courtesy Prof Wollensak
CYTOTOXICITY OF CROSS-LINKING (CXL)
Rabbits irradiated with UVA 370 um
Cornea 2004 2343-49
RiboflavinUVA treatment leads to a dose-dependent
keratocyte damage that can be expected in human corneas
down to a depth of 300u repopulation occurs at 6 months
462016
4
CORNEAL ENDOTHELIAL CYTOTOXICITY OF RIBOFLAVINUVA TREATMENT IN VITRO WOLLENSAK G SPOumlRL E REBER F PILLUNAT L FUNKR
OPHTHALMICRES 2003 NOV-DEC35(6)324-8
A cytotoxic effect on endothelial cells was demonstrated at a
thickness of lt 400um
Patients whose corneas are less than 400um should be excluded for treatment
Endothelial cell culture
YOPRO-stain
Courtesy Prof Wollensak
SLITLAMP APPEARANCE
Early mild diffuse Haze that dissipates with time
Likely due to the linking amp spacing of fibers
6 weeks after corneal collagen
cross-linking reveals bundles
of highly reflective striae
SAFETY OF UVA-RIBOFLAVIN CROSS-LINKING OF THE
CORNEA SPOERL E MROCHEN M SLINEY D TROKEL S SEILER T
CORNEA 2007 MAY26(4)385-9 REVIEW ARTICLE
The currently used UVA radiant exposure of 54 mJcm and the corresponding irradiance of 3 mWcm2 is below the known damage thresholds of UVA for the corneal endothelium lens and retina
CLINICAL STUDIES MAY 2003
22 patients ndash 2 to 4 yrs
no progression in all eyes
Improved in VA in 1522
flattening of Max K by 2D in 1622
eyes
CHANGE OF MAXIMAL K-VALUE
CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-LIGHT IN
KERATOCONUS LONG-TERM RESULTS RAISKUP-WOLF ET AL 2008
J CATARACT REFRACT SURG 2008 796-801) DRESDEN 7-YEARS-RESULTS
Decrease of keratectasia year 1= 27D year 2 = 22D year 3 = 48D
Visual acuity improved by 1 line per year in 54 in first three years
2 patients had continued progression and were x-linked a 2nd time
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
2
in vivo-experiments reveal UV-radiation and riboflavin to be the most effective and the least harmful procedure
Photo+Light Fixitive Sugars
1 Riboflavin (vit B2) + Ultraviolet radiation
2 Production of oxygen radicals
O2-
3 Induction of collagen cross-links -CH2-CH2-CH2-CH = NH-CH2-CH2-CH2-CH2-
collagen fibril collagen fibril
Basics in Crosslinking
Crosslinking
STEPS IN CROSSLINKING (CXL) Calibrate laser
Anesthesia- proparacaine 05
Debride central 7 mm epithelium
Use freshly prepared riboflavin solution (01)(10mg riboflavin-5-phosphate in 10 ml dextran 20 )
Apply every 2 minutes for 30 minutes prior to procedure
Check for Flare in AC
UV radiance of of 3mWcm2
and a wavelength of 370nm ndash 5 cm from eye homogenous
Cornea must be a least 400um
TECHNIQUE
APPLICATION OF RIBOFLAVIN
1 DROP Q 2 MINUTES FOR X 15
RIBOFLAVIN DIFFUSES INTO CORNEAL STROMA
UV RADIATION
U V LIGHT SYSTEM APPEARANCE OF CORNEA DURING UV LIGHT APPLICATION
LABORATORY STUDIES 2003- PRESENT
Biomechanical
Biochemical
Thermal
Morphological
Effect on keratocytes endothelium
462016
3
Crosslinking Extensiometry
RESEARCH - Extensiometry In-Vitro Testing of Corneal Stiffness
Sept 2003
Human Cornea
Porcine Cornea
rarr3289 increase of
rigidity in human cornea
LONG-TERM BIOMECHANICAL PROPERTIES OF RABBIT CORNEA AFTER PHOTODYNAMIC COLLAGEN CROSSLINKING
WOLLENSAK G IOMDINA E ACTA OPHTHALMOL 2008 JUN 11
In the treated rabbit cornea a decrease in
ultimate strain (of 057-784) were found over a
time period of up to 8 months after crosslinking treatment
RiboflavinUVA-induced collagen crosslinking
leads to a long term increase in biomechanical
rigidity which remains stable over time
COLLAGEN FIBER DIAMETER IN RABBIT CORNEAS WOLLENSAK G WILSCH M SPOERL E SEILER T
CORNEA 2004 JUL23(5)503-7
Cross linking using riboflavinUVA leads to a significant increase in corneal collagen diameter
Morphologic correlate of the cross linking process leading to an increase in biomechanical stability
Courtesy
Prof Wollensak
anterior effect
Increase by 12 in fiber diameter
Courtesy Prof Wollensak
CYTOTOXICITY OF CROSS-LINKING (CXL)
Rabbits irradiated with UVA 370 um
Cornea 2004 2343-49
RiboflavinUVA treatment leads to a dose-dependent
keratocyte damage that can be expected in human corneas
down to a depth of 300u repopulation occurs at 6 months
462016
4
CORNEAL ENDOTHELIAL CYTOTOXICITY OF RIBOFLAVINUVA TREATMENT IN VITRO WOLLENSAK G SPOumlRL E REBER F PILLUNAT L FUNKR
OPHTHALMICRES 2003 NOV-DEC35(6)324-8
A cytotoxic effect on endothelial cells was demonstrated at a
thickness of lt 400um
Patients whose corneas are less than 400um should be excluded for treatment
Endothelial cell culture
YOPRO-stain
Courtesy Prof Wollensak
SLITLAMP APPEARANCE
Early mild diffuse Haze that dissipates with time
Likely due to the linking amp spacing of fibers
6 weeks after corneal collagen
cross-linking reveals bundles
of highly reflective striae
SAFETY OF UVA-RIBOFLAVIN CROSS-LINKING OF THE
CORNEA SPOERL E MROCHEN M SLINEY D TROKEL S SEILER T
CORNEA 2007 MAY26(4)385-9 REVIEW ARTICLE
The currently used UVA radiant exposure of 54 mJcm and the corresponding irradiance of 3 mWcm2 is below the known damage thresholds of UVA for the corneal endothelium lens and retina
CLINICAL STUDIES MAY 2003
22 patients ndash 2 to 4 yrs
no progression in all eyes
Improved in VA in 1522
flattening of Max K by 2D in 1622
eyes
CHANGE OF MAXIMAL K-VALUE
CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-LIGHT IN
KERATOCONUS LONG-TERM RESULTS RAISKUP-WOLF ET AL 2008
J CATARACT REFRACT SURG 2008 796-801) DRESDEN 7-YEARS-RESULTS
Decrease of keratectasia year 1= 27D year 2 = 22D year 3 = 48D
Visual acuity improved by 1 line per year in 54 in first three years
2 patients had continued progression and were x-linked a 2nd time
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
3
Crosslinking Extensiometry
RESEARCH - Extensiometry In-Vitro Testing of Corneal Stiffness
Sept 2003
Human Cornea
Porcine Cornea
rarr3289 increase of
rigidity in human cornea
LONG-TERM BIOMECHANICAL PROPERTIES OF RABBIT CORNEA AFTER PHOTODYNAMIC COLLAGEN CROSSLINKING
WOLLENSAK G IOMDINA E ACTA OPHTHALMOL 2008 JUN 11
In the treated rabbit cornea a decrease in
ultimate strain (of 057-784) were found over a
time period of up to 8 months after crosslinking treatment
RiboflavinUVA-induced collagen crosslinking
leads to a long term increase in biomechanical
rigidity which remains stable over time
COLLAGEN FIBER DIAMETER IN RABBIT CORNEAS WOLLENSAK G WILSCH M SPOERL E SEILER T
CORNEA 2004 JUL23(5)503-7
Cross linking using riboflavinUVA leads to a significant increase in corneal collagen diameter
Morphologic correlate of the cross linking process leading to an increase in biomechanical stability
Courtesy
Prof Wollensak
anterior effect
Increase by 12 in fiber diameter
Courtesy Prof Wollensak
CYTOTOXICITY OF CROSS-LINKING (CXL)
Rabbits irradiated with UVA 370 um
Cornea 2004 2343-49
RiboflavinUVA treatment leads to a dose-dependent
keratocyte damage that can be expected in human corneas
down to a depth of 300u repopulation occurs at 6 months
462016
4
CORNEAL ENDOTHELIAL CYTOTOXICITY OF RIBOFLAVINUVA TREATMENT IN VITRO WOLLENSAK G SPOumlRL E REBER F PILLUNAT L FUNKR
OPHTHALMICRES 2003 NOV-DEC35(6)324-8
A cytotoxic effect on endothelial cells was demonstrated at a
thickness of lt 400um
Patients whose corneas are less than 400um should be excluded for treatment
Endothelial cell culture
YOPRO-stain
Courtesy Prof Wollensak
SLITLAMP APPEARANCE
Early mild diffuse Haze that dissipates with time
Likely due to the linking amp spacing of fibers
6 weeks after corneal collagen
cross-linking reveals bundles
of highly reflective striae
SAFETY OF UVA-RIBOFLAVIN CROSS-LINKING OF THE
CORNEA SPOERL E MROCHEN M SLINEY D TROKEL S SEILER T
CORNEA 2007 MAY26(4)385-9 REVIEW ARTICLE
The currently used UVA radiant exposure of 54 mJcm and the corresponding irradiance of 3 mWcm2 is below the known damage thresholds of UVA for the corneal endothelium lens and retina
CLINICAL STUDIES MAY 2003
22 patients ndash 2 to 4 yrs
no progression in all eyes
Improved in VA in 1522
flattening of Max K by 2D in 1622
eyes
CHANGE OF MAXIMAL K-VALUE
CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-LIGHT IN
KERATOCONUS LONG-TERM RESULTS RAISKUP-WOLF ET AL 2008
J CATARACT REFRACT SURG 2008 796-801) DRESDEN 7-YEARS-RESULTS
Decrease of keratectasia year 1= 27D year 2 = 22D year 3 = 48D
Visual acuity improved by 1 line per year in 54 in first three years
2 patients had continued progression and were x-linked a 2nd time
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
4
CORNEAL ENDOTHELIAL CYTOTOXICITY OF RIBOFLAVINUVA TREATMENT IN VITRO WOLLENSAK G SPOumlRL E REBER F PILLUNAT L FUNKR
OPHTHALMICRES 2003 NOV-DEC35(6)324-8
A cytotoxic effect on endothelial cells was demonstrated at a
thickness of lt 400um
Patients whose corneas are less than 400um should be excluded for treatment
Endothelial cell culture
YOPRO-stain
Courtesy Prof Wollensak
SLITLAMP APPEARANCE
Early mild diffuse Haze that dissipates with time
Likely due to the linking amp spacing of fibers
6 weeks after corneal collagen
cross-linking reveals bundles
of highly reflective striae
SAFETY OF UVA-RIBOFLAVIN CROSS-LINKING OF THE
CORNEA SPOERL E MROCHEN M SLINEY D TROKEL S SEILER T
CORNEA 2007 MAY26(4)385-9 REVIEW ARTICLE
The currently used UVA radiant exposure of 54 mJcm and the corresponding irradiance of 3 mWcm2 is below the known damage thresholds of UVA for the corneal endothelium lens and retina
CLINICAL STUDIES MAY 2003
22 patients ndash 2 to 4 yrs
no progression in all eyes
Improved in VA in 1522
flattening of Max K by 2D in 1622
eyes
CHANGE OF MAXIMAL K-VALUE
CROSSLINKING WITH RIBOFLAVIN AND ULTRAVIOLET-LIGHT IN
KERATOCONUS LONG-TERM RESULTS RAISKUP-WOLF ET AL 2008
J CATARACT REFRACT SURG 2008 796-801) DRESDEN 7-YEARS-RESULTS
Decrease of keratectasia year 1= 27D year 2 = 22D year 3 = 48D
Visual acuity improved by 1 line per year in 54 in first three years
2 patients had continued progression and were x-linked a 2nd time
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
5
FIRST PROSPECTIVE RANDOMIZED CLINICAL TRIAL OF CROSSLINKING FOR KERATOCONUS
Progressive Keratoconus defined by increase in
Kmax by 10 D MR cyl by 10 D
MRSE by 05 D CL base curve by 01 mm
Exclusion for lt400 um scars or previous surgery
J Refract Surg 2008 (Sept) 24(7) S720-5
RISK FACTORSCOMPLICATION RATES SEILER 2009 117 EYES
Eyes losing gt2 lines BSCVA = 29
Continued progression after CXL =76
Sterile infiltrates 76
Central stromal scars 28
RARE CORNEAL HAZE COMPLICATION
USUALLY CLEARS SLOWLY OVER
TIME
SLIT LAMP APPEARANCE OCT STUDY
SHOULD EPITEHLIUM BE REMOVED
CURRENT CONSENSUS - YES 1 Research by Wollensak - 28 effect
2 Confocal Mic - no effect under epith
3 OCT - shows no changes wth epi on
4 Dangers of UV light without uniform absorption
5 Can use removing epithelium to your advantage
IMMUNOFLUORESCENT STAINING CONFOCAL (BOTTOS SCHOR amp CHAMON)
No stromal compaction
in presence of epithelium
or without UVA or Riboflavin
J Refract Surg 2008 (Sept) 24(7) S715-9
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
6
ABSTRACT PURPOSE To present data on unhappy keratoconus patients
who presented to our office following C3R ldquoepi-onrdquo cross-linking
METHODS Retrospective chart review 1 year post procedure
RESULTS 13 eyes were identified Mean age was 33 yrs
(range 23 ndash 41) Mean uncorrected acuity was 20200
(range 2040-20200) Mean best-corrected acuity was 2060
(range 2030-20200) Mean central pachymetry was 435um
(range 380-485) Mean K value was 5027(range 43-58)
Mean I-S value was 425(range 184-1086) 4 eyes had
repeat cross-linking with the standard epi-off procedure 4 eyes
had corneal transplants and 5 eyes had no further treatment
CONCLUSIONS These data suggest that the ldquoepi-onrdquo C3R
procedure may not be optimal for treating keratoconus
EYE 2 - PRE OP AND 1 YEAR POST OP TOPOGRAPHY C3R - 8 D CHANGE
RESULTS
SUMMARY OF FINDINGS AT
PRESENTATION
413 (30) eyes had paracentral scars
913 (70) eyes had 1 additional surgery
613 (46) eyes had 2 additional surgeries
313 (23) eyes had 3 additional surgeries
CORNEAL CROSSLINKING (CXL) SINGLE CENTER CLINICAL TRIAL(IDE FROM FDA) - CXL VS INTACS + CXL
Currently enrolling patients
400 patients randomized to INTACS and no INTACS
Must Exhibit 1D of progression in past year
Can have Keratoconus or Ectasia after LASIK
For more information go to
wwwkeratoconuscom
EXCLUSION CRITERIA FOR CLX Corneas thinner than 400u
K reading of gt58D
Central corneal scar
Age gt 35 years stable
Preoperative BSCVA 2025 or better
Autoimmune disease Herpes Pregnant
Unrealistic expectations
ENTRY CRITERIA
18 years of age
Keratoconus or Ectasia
Demonstrate progression of Keratoconus in past year
Cornea must - 400um thick
K reading less than 58D
No central or paracentral scarring
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
7
COLLAGEN CROSSLINKING RESULTS 12 MONTHS
PROGRESSIVE KERATOCONUS (N=77) CORNEA EYE INSTITUTE (JULY 2011--DR RABNINOWITZ)
UCVA BSCVA Average K
Gain in lines Gain in lines flattening
Mean 135 Mean 025 Mean 031D
Range -2 to 5 Range -2 to 4 Range -8 to 4
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY AVERAGE K CORNEA EYE INSTITUTE
(JULY 2011)
93 flattened or did not change
62 flattened by 05D or more
31 did not change
15 steepened by 05D or more
COLLAGEN CROSSLINKING RESULTS 12 MONTHS - SUMMARY ACUITY CORNEA EYE INSTITUTE
(JUNE 2011)
61 of patients gained at least 1 line of acuity
42 of patients gained at least 2 lines of acuity
15 of patients lost at least 1 line of acuity
Prospective Randomized Study ndash 1 year results
Standard CXL vs Sham group( 70 eyes)rsquo
J Cat Ref Surg January 2011 Hersh PS et al
UCVA improved (20137) to (20117) (P = 04)
BSCVA improved (2045) to (2034) (Plt001)
211 gained and 14) 2 or more Snellen lines
Max K value decreased by 17 plusmn 39 diopters (D) (Plt001)
Max K decreased by 20D (310) increased by 20 D (42)
Keratoconus patients did better than ectasia patients
TOPOGRAPHY DRIVEN PRK + CORNEAL CROSSLINKING NOT APPROVED IN THE US
DR JOHN KANELLOPOULOS
NEW YORK AND ATHENS GREECE
ldquoTOPO LINK PRKrdquo TOPO LINK PRK + CXL
INDIAN JOURNAL OF OPHTHALMOLOGY 2014
PRE AND POSTOP TOPOGRAPHY OF PT IN INDIA OCT FROM PATIENT IN INDIA
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE
462016
8
THANK YOU FOR YOUR ATTENTION
CROSSLINKING IS A MAJOR ADVANCE
THAT WILL DECREASE THE NEED FOR CORNEAL TRANSPLANTS FOR
THOUSANDS OF PATIENTS WORLD WIDE