Ophthalmology Lectures: Corneal crosslinking is the only way approved to stop progression of Keratoconus,,let's review the old & new methods of crosslinking

1. one way to optimize
corneal cross linking !!
Dr.Diyar jaafer
C.A.B.(Ophth),FICO
Ibn Alhaitham Teaching Eye Hospital

2. Financial Disclosure
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There are no financial disclosures relevant to
this presentation

3. CROSSLINKING (CXL)
is a technique which uses UV light and
aphotosensitizer to strengthen chemical bonds in the
cornea.
In 1998, corneal collagen cross-linking was first
proposed as a treatment modality to stabilize the
ectatic cornea.
The standard Dresden protocol entails UV-A
treatment over a central 9 mm zone at an irradiance of
3.0 mW/cm2 for 30 min, delivering a fluence of 5.4
J/cm2
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5. Patient Characteristics Predictive of
Corneal Flattening After Cross-linking
▪ For the same cross-linking
parameters, variability in
the change in Kmax
predicted by:
• Initial Kmax
• Cone Location
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Significant corneal flattening observed in 40%
of cases. The only factor that was
independently predictive of flattening was
baseline Kmax of greater than 54.00 D
Koller T, Pajic B, Vinciguerra P, et al.
Flattening of the cornea after collagen
crosslinking for keratoconus. J Cataract
Refract Surg. 2011;37(8):1488–92.
The only evaluated factors independently
predictive of improvement after CXL were
CDVA of 20/40 or worse, or KMax of 55.00 D
or greater.
Greenstein S a, Hersh PS. Characteristics
influencing outcomes of corneal collagen
crosslinking for keratoconus and ectasia:
Implications for patient selection. J
Cataract Refract Surg. 2013;39(8):1133–40
Baseline KMax was not predictive of cross-
linking outcome in this study. However, a
more eccentric cone was associated with
steeper keratometry at 1 year follow-up.
Wisse RPL, Godefrooij D a, Soeters N, et al.
A Multivariate Analysis and Statistical
Model for Predicting Visual Acuity and
Keratometry One Year After Cross-linking
for Keratoconus. Am J Ophthalmol.
2014;157(3):519–525.e2

6. Major drawback :
▪ 1. Time
▪ 2. Epi. Off related complication
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7. Epi. off VS Epi. on
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Gray

8. But Epi. On still in mind…..
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9. 1. chemical modifications to riboflavin, such as
addition of enhancers (EDTA, benzalkonium
chloride or 20% alcohol),Ricrolin TE®, which
combines two enhancers: amino alcohol and
EDTA.
2. the iontophoresis technique, a noninvasive
procedure during which a low-intensity electric
current is applied to enhance the penetration of
riboflavin into the stroma, stands out as being
as efficient as conventional application of
riboflavin, based on a pre-clinical study
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10. Giuliano Scarcelli, PhD, and colleagues who
evaluated the mechanical properties of keratoconic
corneas using tissue removed during keratoplasty
Using Brillouin optical microscopy, they showed
mechanical loss was generally localized to
the area of the cone, whereas outside the cone
the Brillouin shift was similar to that measured in
healthy control eyes
concept of performing customized CXL arose from
findings of biomechanical modeling undertaken by
Abhijit Sinha Roy, PhD, and William J. Dupps Jr., MD,
PhD, who proposed that the biomechanical
change in keratoconus is focal, not
generalized
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One way to optimize
corneal CXL :
Customize it

13. Customized CXL is a tomography-guided procedure that
focuses the treatment on the weak area of the keratoconic cornea. The
procedure, which Avedro has been marketing as CuRV, is performed
using a proprietary adjustable ultraviolet A light device (Mosaic
System, Avedro) that features an integrated eye tracker and enables
projection of customized irradiation patterns with customized energy
profiles onto the cornea .
In C-CXL, the corneal stroma is soaked with a riboflavin solution
before exposure to a uniform beam of UV-A radiation. Targeting the
CXL procedure to stiffen this area specifically represents an
interesting strategy to redistribute biomechanical stresses in the
cornea Transition headline
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14. Customized CXL for
treatment
ofKeratoconus
Prof. Theo Seiler
Prospective evaluation of
customized CXL
versus conventional
cross-linking
10 minute VibeX Rapid Soak
10mW/cm2 continuous
illumination in custom group
Concentric superimposed circular
zones applied
Treatment zone centered on posterior
float
Treatment doses ranging from 5.4 to
10 J
Dresden CXL in conventional group
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15. ▪ inner circle: total energy applied 10J/cm2 – shortest diameter of
PF – 0.5mm
intermediate circle: total energy applied 7.2J/cm2 – average
diameter of outer/inner circle
outer circle: total energy applied 5.4J/cm2 - maximal diameter
of PF + 1.0 mm
.
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p-valuestandard
CXL
customized
CXL
0.03-0.9 ± 1.3-1.7 ± 2.0Δ Kmax [D]
0.034.1 ± 3.15.2 ± 2.7regularization index
[D]
0.023.19 ± 0.732.56 ± 0.5epithelial healing
time [days]
0.22-0.04 ± 0.14-0.07 ± 0.20Δ -logMAR
significant differences in 1 year changes between groups

17. Evolutive keratoconus treated by customized topography-guided
corneal cross-linking: clinical results
Author:M.Cassagne FRANCE
CoAuthor(s): K.Pierne S.Galiacy P.Fournie F.Malecaze
Acustomized CXL technique for keratoconus that concentrates on the
area of the cone shows promise for stabilizing the cornea and for
improving vision.
François Malecaze, MD, PhD; and Kévin Pierné, FRCOphth
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Customized CXL for treatment of Keratoconus
Cosimo Mazzotta, Antonio Moramarco, Claudio Traversi,
Stefano Baiocchi, Alfonso Iovieno, and Luigi Fontana
Italian Multicenter Study of Customized CXL for Treatment
of Keratoconus

18. Look For :
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1. Epithelial healing
2. Maximum keratometry
Mean change in Kmax
for the customized and
standard groups was –1.7
D and –0.9 D

19. 3. Corneal reshaping. the mean regularization index
values for the two groups were 5.2 D and 4.1 D,
4. Visual acuity .CDVA improved to 0.2648 ±0.2574 logMAR
(P=.104) in the C-CXL eyes, compared with 0.2162 ±0.2495 logMAR
(P<.05) in the TG-CXL eyes
5. Safety
6. Nerve and cell density
7. demarcation line depth
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PiXL
customized crosslinking induces changes in
corneal curvature by adding strength. The
application of customized U-VA illumination
patterns for the treatment of refractive error
through zone-specific crosslinking has been
termedphotorefractive intrastromal crosslinking,
or PiXL

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AT A GLANCE
• Biomechanical analyses of keratoconic corneas have shown
that weakening is concentrated within the area of the cone.
• Targeting the CXL procedure to stiffen the area of the
keratoconic cone specifically represents one strategy to
redistribute biomechanical stresses in the cornea.
• Topography-guided CXL has been shown to induce a
flattening effect that is greater than the effect of conventional
CXL and also produce a gradient in the biological response to
treatment from the area of the cone to the surrounding area.

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