1. Effects of corneal collagen crosslinking on Ocular Response Analyzer waveform-derived variables in keratoconus and post-LASIK ectasia
Spatial treatment comment after cone localization slide.
William J. Dupps, Jr., M.D., Ph.D.
Karolinne Maia Rocha, M.D., Ph.D.
Katie Hallahan, B.S.
Abhijit Sinha Roy, Ph.D.
J. Bradley Randleman, M.D.
R. Doyle Stulting, M.D., Ph.D.
Emory University
Dr. Stulting is medical monitor for the FDA crosslinking study.

2. Acknowledgments Support: RPB Career Development Award
NIH/NCRR K12/KL2RR024990
National Keratoconus Foundation
Cleveland Clinic Innovations Product Development Fund
Clinical data collection supported through sponsored FDA study (IROC)

3. Crosslinking for keratoconus (KC)
Non-enzymatic collagen stiffening with riboflavin and UVA light
Wollensak et al, AJO, 2003

4. Ocular Response Analyzer
Provides a dynamic, air impulse-driven spatio-temporal history of the central corneal bending response (Luce, J Cataract Refract Surg, 2005)
Corneal hysteresis (CH) and corneal resistance factor (CRF) no different on average after crosslinking in 10 KC eyes (Goldich et al, Cornea 2009)

5. Does this mean the ORA cannot detect CXL changes (or that there are no changes?)
Purpose
To investigate waveform-derived variables as more sensitive/specific indicators of CXL effect
Custom analysis variable categories:
Absolute and relative timing of events
Signal intensities
Pressure/applanation signal relationships (stress/displacement analogue)
Plug into Manu’s paper
Hallahan et al, ARVO 2008

6. Methods: ORA analysis from FDA crosslinking study
Patients with progressive keratoconus (24 eyes of 20 patients) or post-refractive surgery ectasia (31 eyes of 24 patients)
Replicate ORA measurements before & 3 months after epithelium-off crosslinking (UV-X, IROC)
Pre-treatment and post-treatment waveform variables analyzed for pairwise differences (paired student’s t-tests)
(prostate, breast, liver) Can you tell by looking at it?

7. ORA changes with crosslinking in post-refractive surgery ectasia
NO significant changes in CH, CRF, but...
Peak 1 onset time (POT) increased (p=.002)
Concavity time (CT) shorter (p=.04)
1st and 2nd applanation events higher (p<.004)
Changes in 5 of 39 Reichert beta ORA variables
aindex, w11, dive1, aplhf, P1 and P2 (p<.05)
(prostate, breast, liver) Can you tell by looking at it?

8. ORA changes with crosslinking in post-refractive surgery ectasia
(prostate, breast, liver) Can you tell by looking at it?
Increase in Pmax
Earlier/shallower recovery from concavity
Delay in peak 1

9. Conclusions No changes in standard ORA variables
But significant changes in temporal and amplitude responses did occur after crosslinking in post-refractive surgery ectasia patients:
Changes are consistent with increased corneal bending resistance and a shallower, more rapid recovery from air puff deformation with greater pressures required to achieve applanation
No significant changes in the same variables were seen after crosslinking in this sample of KC patients; further analysis of this group is underway
(prostate, breast, liver) Can you tell by looking at it?

10. Thank you