This document summarizes results from three studies comparing treatments for keratoconus: femtosecond laser-assisted circular keratotomy (FSCKT), corneal crosslinking (CXL), and iontophoresis-assisted corneal crosslinking (ICXL). FSCKT showed improvement in best-corrected visual acuity over 3 years with stable corneal thickness, keratometry, and ectasia values. CXL showed improvements in all outcomes over 5 years. ICXL results after 1 year were less clear, with no significant changes observed. The document concludes CXL may be most effective but longer-term ICXL data is needed, and direct comparative studies could improve comparisons between treatments.

1. Breyer, Kaymak & Klabe Eye Surgery and Premium Eyes are Consulting, Study Center & MAB for:
Abott, Alcon, AlimeraSciences, Allergan, AMO, Bayer, Carl Zeiss Meditec, Ellex, Fluoron, Geuder,
iOptics, LensAR, Medicem, Novartis, Oculentis, Oertli, Revision Optics, Santen, Staar Surgical,
Sifi Medtech, Thea, Topcon, Visufarma, Ziemer
Three-Years Results after Femtosecond laser-assisted Circular Keratotomy
as a Treatment for Keratoconus Stage I-II.
Comparison with (Iontophoresis-Assisted) Corneal Crosslinking.
D. Breyer, H. Kaymak, K. Klabe, P. Hagen, T. Ax, F. Kretz, G. Auffarth
Breyer, Kaymak & Klabe Eye Surgery and Premium Eyes are Consulting, Study Center & MAB for:
Abott, Alcon, AlimeraSciences, Allergan, Bayer, Carl Zeiss Meditec, Ellex, Fluoron, Geuder, iOptics,
Johnson&Johnson, LensAR, Medicem, Novartis, Oculentis, Oertli, Revision Optics, Santen, Staar
Surgical, Sifi Medtech, Thea, Topcon, Visufarma, Ziemer

2. • Degenerative eye disease
• Progressive thinning and steepening of cornea as well as increased stability loss
• Can lead to severe degradation of visual acuity
Keratoconus
Retrospective analysis of results in different treatment groups
Circular keratotomy via
femtosecond laser
Corneal crosslinking
Iontophorese-assisted
corneal crosslinking
FSCKT (up to 3 years) CXL (up to 5 years) ICXL (up to 1 year)

3. • Most used treatment for progressive keratectasia
• Epithelium is removed
• Cornea is soaked with riboflavin
• Exposure to UV-A light source
• Increase in corneal stability is proven in numerous studies
• Standard parameters: Dresden protocol
1O2 interacts with
stromal components
 Increase in
degree of
stromal cross-
linking
Corneal Crosslinking
(CXL)
• complex photochemical reaction
• transformation of free oxygen O2 into excited
singlett-state 1O2
Riboflavin
+ UV-A
+ O2

4. • Novel method through modification of CXL
• Epithelium remains intact
• Riboflavin ions overcome epithelium barrier by application of an electric field between affixed
anode and cathode grid within riboflavin solution
• Afterwards: exposure to UV-A light
• Efficacy in decrease of progression could be shown
• Presumably slightly less effective than CXL
Iontophorese-assited Corneal Crosslinking
(ICXL)
first author year follow-up #eyes BCDVA Kmax
Jia H-Z 2017 24M 94 + +
Bikbova G 2016 24M 76 +
Buzzonetti L 2015 15M 14 + 0
Bikbova G 2014 12M 22 + +
Vinciguerra P 2014 12M 20 + 0

5. Circular Keratotomy
(CKT)
• Treatment for keratoconus of grade I and II
• Circular cut via trephine knife
• Double-running anti-torque suture
• Cut mechanically isolates central cornea  Surface becomes more spherical
• Desired effect: scar acts like a stabilizing ring

6. • Further development of CKT
• Treatment for keratoconus of grade I and II
• Ring-shaped purely intrastromal cut via femtolaser (Ziemer FEMTO LDV Z6)
 from 100 µm below epithelium to 60 µm above Descemet’s membrane
 Advantages: Sutureless, higher speed of operation, less pain sensation
• Desired effect: intrastromal scar acts like a stabilizing ring
Cornea
Intrastromal ring-shaped cut
Circular Keratotomy via Femtosecond Laser
(FSCKT)

7. Group FSCKT CXL ICXL
number of eyes 10 118 100
age [years] 39.4 ± 6.6 31.9 ± 10.6 30.4 ± 11.1
♀ : ♂ [%] 100:0 74:26 79:21
BCDVA [logMAR] 0.00 ± 0.06 0.42 ± 0.30 0.30 ± 0.22
Corneal thickness
(thinnest point) [µm]
505 ± 41 470 ± 49 492 ± 35
Kmax [D] 47.8 ± 2.5 55.6 ± 7.8 51.8 ± 5.0
BAD-D 3.9 ± 1.8 8.8 ± 4.8 8.2 ± 3.5
Materials and Methods: Preoperative Patient Data
• Significant and clinically relevant differences in preoperative parameters
 No direct intergroup comparison possible but rather
 Observation of postoperative results and tendencies for each group

8. -0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
pre 6M 1Y 3Y 5Y
BCDVA[logMAR]
Monocular bestcorrected VA at far
Results: BCDVA
#eyes
pre 6M 1Y 3Y 5Y
M ± SD
FSCKT
10 10 9 9 (4)
0.00 ± 0.06 -0.06 ± 0.06 -0.07 ± 0.04 0.00 ± 0.09 0.00 ± 0.00
CXL
106 59 53 28 15
0.42 ± 0.30 0.32 ± 0.24 0.27 ± 0.28 0.17 ± 0.21 0.20 ± 0.15
ICXL
94 47 (9)
0.30 ± 0.22 0.23 ± 0.33 0.38 ± 0.21
Significant (p<0.05) improvement at all
postoperative visits compared to
preop.
Significant (p<0.05)
improvement at 6M and 1Y
Change at 1Y not yet significant
VA measurement
(ETDRS chart + phoropter)
( )
( )

9. 400
420
440
460
480
500
520
540
560
pre 6M 1Y 3Y 5Y
ThinnestPoint[µm]
Corneal Thickness at Thinnest Point #eyes
pre 6M 1Y 3Y 5Y
M ± SD
FSCKT
10 10 9 9
505 ± 41 507 ± 39 501 ± 39 507 ± 43
CXL
104 78 54 24 16
470 ± 49 446 ± 45 466 ± 43 474 ± 47 476 ± 53
ICXL
95 78 (12)
492 ± 35 490 ± 34 486 ± 27
Results: Pachymetry
• Significant (p<0.05) thinning at 6M
as consequence of epithelium
removal?!
• Subsequent return to initial level
Stable values
Change at 1Y
not yet significant
Scheimpflug tomography
(Pentacam HR, Oculus)
( )

10. 45
47
49
51
53
55
57
59
61
63
65
pre 6M 1Y 3Y 5Y
Kmax[D]
Steepest sagittal meridian (Kmax)
Results: Keratometry
#eyes
pre 6M 1Y 3Y 5Y
M ± SD
FSCKT
10 10 9 9
47.8 ± 2.5 47.9 ± 2.6 48.0 ± 2.3 47.9 ± 2.3
CXL
104 78 54 24 16
55.6 ± 7.8 56.3 ± 7.4 54.3 ± 6.5 53.7 ± 6.7 51.5 ± 6.5
ICXL
95 78 (12)
51.8 ± 5.0 52.0 ± 5.0 54.4 ± 6.1
Scheimpflug tomography
(Pentacam HR, Oculus)
Significant (p<0.05) flatterning at
3Y and 5Y compared to preop.
Stable values
( )
Changes at 1Y
not yet significant

11. 0
2
4
6
8
10
12
14
pre 6M 1Y 3Y 5Y
BAD-D
Belin Ambrósio Enhanced Ectasia
Results: Belin Ambrósio Enhanced Ectasia
#eyes
pre 6M 1Y 3Y 5Y
M ± SD
FSCKT
10 10 9 9
3.9 ± 1.8 3.6 ± 1.8 3.4 ± 1.5 3.7 ± 1.9
CXL
104 78 54 24 16
8.8 ± 4.8 9.6 ± 4.3 8.0 ± 3.2 7.8 ± 3.8 6.6 ± 4.2
ICXL
95 78 (12)
6.2 ± 3.1 6.4 ± 3.2 8.2 ± 3.5
Significant (p<0.05) improvement
at 1Y and 5Y compared to 6M
Stable values
Scheimpflug tomography
(Pentacam HR, Oculus)
( )
Change at 1Y
not yet significant

12. Summary
+ = improvement
Longest
follow-up
BCDVA
Corneal
thickness
Kmax BAD-D
0 = stable values
- = worsening
* = significant (p<0.05)
FSCKT 3Y
+ 0 0 0
*
CXL 5Y
+ 0 + +
* * *
ICXL 1Y
0/- 0/- 0/- 0/-
• Observed tendencies in efficiency:
„CXL > FSCKT > ICXL“
• CXL: Observed improvements
comparable to literature values

13. Summary
+ = improvement
Longest
follow-up
BCDVA
Corneal
thickness
Kmax BAD-D
0 = stable values
- = worsening
* = significant (p<0.05)
FSCKT 3Y
+ 0 0 0
*
CXL 5Y
+ 0 + +
* * *
ICXL 1Y
0/- 0/- 0/- 0/-
• ICXL: Only a treatment for grade I (and II)
 Increase irradiation period:
 more time for oxygen diffusion
 compensates for epithelial UV-absorbance

14. Summary
+ = improvement
Longest
follow-up
BCDVA
Corneal
thickness
Kmax BAD-D
0 = stable values
- = worsening
* = significant (p<0.05)
FSCKT 3Y
+ 0 0 0
*
CXL 5Y
+ 0 + +
* * *
ICXL 1Y
0/- 0/- 0/- 0/-
• ICXL 1-year data must be interpreted with caution larger data set and longer follow-up needed
• Improving comparability
 prospective, randomized comparative study or
 retrospective analysis with matching of preoperative patient data

15. Thank you very much for your attention!
Partner of