Northern Colorado Eye Center
Continuing Education Event
Corneal Collagen Cross-linking
September 20, 2014
S. Lance Forstot, MD, FACS
Corneal Consultants of Colorado
Founding Partner
Clinical Professor of Ophthalmology
University of Colorado Medical School
Ultraviolet Light
• UVC
– 220-290nm
– Blocked by ozone layer
• UVB
– 290-320nm
• UVA
– 320-340nm
Ultraviolet Light
• UVA
– Can induce corneal endothelial damage
with surface dose of 42.5 J/cm2
– Typical dose for CXL only 5.4 J/cm2
– Estimated dose received by cornea in
15-20 min of sun exposure on a summer
day
Real World UV
Hawaii in Spring
Australia in Summer
All Exposed Tissues:
 Spring 170-200J/cm2/day in 3-4 hrs outdoors
 Fall ~60J/cm2/day of solar UVA
Cornea:
 5J/cm2 in 15-20 min in Summer
Safety of Cross-Linking
Endothelium
Damage threshold
3.00 mW/cm²
0μm
100%
3.00 mW/cm²
100μm
50%
1.49 mW/cm²
200μm
25%
0.74 mW/cm²
300μm
12%
0.36 mW/cm²
400μm
6%
0.18 mW/cm²
500μm
3%
0.09mW/cm²
0.06
600μm
2%
mW/cm²
How much UV – light gets into the
eye ?
70 J/cm2
0.65 J/cm2
5.4 J/cm2
Radiant exposures
0.46 J/cm2 (9 %)
0.33 J/cm2 (7 %)
0.14 J/cm2 (2.1%)
0.12 J/cm2 (1.9%)
Radiant Energy is
Below Damage
Threshold
Damage thresholds
70 J/cm2
7.7 J/cm2
Safety of UVA-Riboflavin
Cross-Linking of the Cornea
Min pach of
400 μm
protects
endothelium,
lens, retina
300 µ
Spoerl, et. al Cornea 2007; 26:385-389
Riboflavin (Vitamin B2)
• Critical role in CXL
• Increases UVA absorption to 95% in
saturated corneas (versus 32%
w/o)
Riboflavin
Diabetics, KCN and CXL
Diabetics don’t
often develop adv
KCN because of
natural cross-linking
from sugars and UV
light
Seiler T, Huhle S, Spoerl E, Manifest Diabetes
and Keratoconus, Graefe’s Arch 2000
CXL – UVA+Riboflavin
• Results in increase in biomechanical
rigidity (stiffening)
• Strongest effect in anterior 300u
– Which plays major role in
maintaining corneal curvature
• Results in corneal flattening and and
reduction in spherical equivalent
CXL with Riboflavin
Stiffened Cornea
• ↑Rigidity
• In Europe since
1998
• New Tx in US
• KCN, pellucid,
ectasia, post-RK
Normal Cornea
Scanning Electron
Microscopy
CXL
• Mechanism
– Not completely understood
– Riboflavin known to generate active
oxygen species (singlet oxygen and
superoxide anion radicals)
Confocal Microscopy
Pre op
1 m postop
3 m postop
• Apoptosis 300 μm deep after
CXL
• Repopulation takes 6 months
6 m postop
Courtesy of Dr.
Caporossi,
Crosslinks Between Collagen Fibers
Strengthens Cornea like Ladder
Rungs
Cross-Linking is Not New
• Hardening of polymers in
materials science since
1930s
(silicone oil→rubber ball)
• Dentists XL for decades
• Normal aging of connective
tissue involves cross-linking
and stiffening
• KCN progression ↓ with age
We All “Crosslink” as we Grow Up
History of CXL
• Basic research 1993-97
by Seiler & Spoerl
• First patients Txd in 1999
• Today over 400 centers
worldwide
• Standard of care for KCN
(in Europe as young as 9)
CXL Technique
•
•
•
•
•
Anesthetic drops, painless
Prepare cornea
Riboflavin drops for 30 mins
UV light for 30 mins
Bandage contact lens
Riboflavin 0.1% Drops
Patient’s View of UV Light
UV-A Light
CXL & Curvature Change
Change in avg or steep
K does not provide key
info
See diff maps to
appreciate true
curvature changes
Preop
Postop 11 M
Difference Map
3D
Flatter
5D
Steeper
Preop
450 um
6 M Postop
411 um ( 8.6%)
Pachymetry Maps
9 M Postop
429 um
12 M Postop
450 um
56 yr old male with Keratoconus: Epi-On CXL OS
Pre Op
6 months Post
Op
UCVA
CF
100
BSCVA
25
20
Refraction
-7.75+0.75x150
-3.75 +1.50 x
180
6 months
Preop
Difference Map
William Trattler, MD case
CXL: Epi-On v. Epi-Off
Epi-On Crosslinking for Ectasia
38 year-old male with post-Lasik ectasia
OD
UCVA
Refraction
BSCVA
Pre Op
200
-3.50+6.50x180
30
3 Months
50
-0.75+1.75x175
25
Post Op 3 Months
Pre Op
Difference Map
William Trattler, MD case
BSCVA Comparison
BSCVA Comparison
Summary of Epi-ON
• EPI-On CXL
– Benefits:
• Faster visual recovery/less pain
• Reduced risk of pain/haze
• Very good clinical results
– Even in keratoconus patients over the age of 35
– Downside:
• Longer procedure (30-50 min longer)
• Can not combine with simultaneous topo-guided
PRK
William Trattler, MD
Final Points
• Epi-On can be as effective as Epi-Off
– Technique differences can explain differences in
results
• Age is not a major factor
– Older patients can benefit from crosslinking
• Progression is not required for successful results with
crosslinking
– Non-progressive patients can achieve improvement in
corneal shape, UCVA, and BSCVA
Long-term Results
•
•
•
•
•
•
241 eyes
Follow-up 6 months to 6 years
Flattening: 2.68 D at 1 year; 4.84D at 3 years
BCVA improvement (> 1 line): 53% at 1 year
No BCVA lines lost
2 patients had KCN prog and repeat CXL
Raiskup-Wolf, Hoyer, Spoerl.
J Cat Ref Surg May 2008
(Also AJO April 2010)
Long Term Results
 5 year study, 48 eyes (60 pts treated)
 No patient had prog of keratectasia.
 Postop avg improvement 2.87 D
 Improvement in BCSVA by 1.4 lines
Wollensak G. Crosslinking treatment of progressive keratoconus: New hope.
Curr Opin Ophthalmol. 2006 Aug;17:356-60
CXL for KCN, Ectasia
•
•
•
•
Shown safe and effective worldwide
Arrests KCN progression (95+%)
UCV, BCSVA, CL tolerance ↑ (60-80%)
Ideal candidates ≤ 45 y/o, corneal
thickness ≥ 400 µm, limited scarring
• Minimum age in Europe now 9 y/o
CXL Complications
•
•
•
•
•
Infectious keratitis – bacterial, fungal
Sterile ulceration
Corneal haze
HSV keratitis
Corneal edema
After CXL
•
•
•
•
Ring segments
PRK
Topo-guided PRK
Better PKP Results?
Topographically-Guided Ablation
 Developed by Theo
Seiler
 Over 22,000 curvature
points on the cornea
 Linked to excimer laser
 Main indications irreg
astig, decentered
ablations, small OZ
Topography
Ablation
More tissue
removed
CXL
Other Applications
– Corneal edema
– Infectious Keratitis
– Radial Keratotomy
CXL and Ortho-K
CXL and the FDA
•
•
•
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Current status -Investigational
Physician IND
IRB Trials
FDA Trials
Thank you for your attention
S. Lance Forstot, MD, FACS
• www. corneacolorado.com
• SL4STOT@aol.com