Effects of corneal collagen crosslinking on Ocular Response Analyzer waveform-derived variables in keratoconus and post-

1. Effects of corneal collagen crosslinking on Ocular Response Analyzer waveform-derived variables in keratoconus and post-LASIK ectasia 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) 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)

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) • Pressure @ 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)

8. ORA changes with crosslinking in post-refractive surgery ectasia 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

10. Thank you