Ocular Response Analyzer Waveform Analysis in the Ectatic Corneas: Correlation of the New Corneal Biomechanics Parameters and Severity of Keratoconus Kristin M. Hammersmith, MD, Peter R. Laibson, MD, Christopher J. Rapuano, MD Teeravee Hongyok, MD, Elisabeth J. Cohen, MD, Kristin M. Hammersmith, MD, Peter R. Laibson, MD, Christopher J. Rapuano, MD Cornea Service, Wills Eye Institute Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA The authors have no financial interest in the subject matter for this poster. World Cornea Congress VI, Boston, MA, USA, April 7-9, 2010

Introduction Ocular Response Analyzer (ORA) measurements of biomechanical properties of the cornea may be another helpful tool to help detect early keratoconus and aid in disease classification. Corneal hysteresis (CH) and corneal resistance factor (CRF) are significantly lower in keratoconic eyes compared to normal eyes, but the values overlap and can not distinguish between mild keratoconus and normal, when used alone. 1, 2 The ORA signal waveforms differ from normal waveforms in many ways, such as lower amplitude of applanation peaks in ectatic corneas compared to normals. 3 1 Luce DA. J Cataract Refract Surg 2005;31(1): Kirwan C, et. al. Ophthalmologica 2008;222(5): Kerautret J, J Cataract Refract Surg 2008;34(3):510-3.

New ORA Waveform Parameters With new software (version 2.04), the ORA can mathematically describe waveform morphological characteristics including signal peak, width, slope, area under the curve, noise, and aspect ratio (height/width) of the waveform. We describe the new waveform parameters in figures below and tables in the following slide. Fig.1 * Fig.2 ** Fig.3 ***Fig.4 ***

Parameter NameDescription From 75% of Applanation Peak* From 50% of Applanation Peak** Aindex-“smoothness” or degree of "non- monotonicity" or number of breaks when peak changes direction in peak 1 Bindex-“smoothness” or degree of "non- monotonicity" or number of breaks when peak changes direction in peak 2 P1areaP1area1area under the curve of peak1 (sum of values) P2areaP2area1area under the curve of peak2 (sum of values) Aspect1Aspect11aspect ratio (height/width) of peak1 Aspect2Aspect21aspect ratio (height/width) of peak2 Uslope1Uslope11rate of increase from base to peak value of peak 1 Uslope2***Uslope21***rate of increase from base to peak value of peak 2 (downslope in real time of peak2) *** Dslope1Dslope11rate of decrease from peak to base value of peak 1 Dslope2***Dslope21***rate of decrease from peak to base value of peak 2 (upslope in real time of peak2) *** W1W11width of peak1 at "base" of peak1 region W2W21width of peak2 at "base" of peak2 region Parameter NameDescription From 75% of Applanatio n Peak* From 50% of Applanation Peak** H1H11height (from lowest to highest value) of peak1 H2H21height (from lowest to highest value) of peak2 Dive1-absolute value of monotonic decrease on downslope part of peak1 starting at the peak value Dive2***-absolute value of monotonic decrease on downslope part of peak2 starting at the peak value Path1Path11absolute value of path length around peak1 Path2Path21absolute value of path length around peak2 Mslew1-maximum single step increase in rise of peak1 (longest continuous line without a break) Mslew2***-maximum single step increase in rise of peak2 Slew1-aspect ratio of dive1 (value of dive divided by width of dive region) Slew2***-aspect ratio of dive2 (value of dive divided by width of dive region) Aplhf-high frequency "noise" in region between peaks (normalized by product of average of peak heights times width of region) Waveform Score (WS)The overall score calculated from these parameters using neural network. 15 Higher score represents a better waveform and more reliable measurement. *Data are analyzed from upper 75% of the applanation peak (Fig. 1 ) **Data are analyzed from upper 50% of the applanation peak (Fig. 2) ***The data from the second applanation were analyzed in time-reversed fashion (Fig.3,4)

Purpose To evaluate the correlation between the Ocular Response Analyzer (ORA) signal morphology using new waveform parameters and severity of disease in eyes with keratoconus and pellucid marginal degeneration.

Methods Patients diagnosed with keratoconus and pellucid marginal degeneration on the Wills Eye Institute Cornea Service from March 2007 to April 2008 were prospectively enrolled in a study of patients with glaucoma or suspect glaucoma and age-matched controls. (Cohen EJ.,Trans Am Ophthalmol Soc Dec;107: ) Eyes with previous ocular surgery or hydrops were excluded. Clinical and demographic characteristics were recorded. The corneal biomechanics were measured using the ORA with new software version Corneal curvature and central thickness were measured using Humphrey® Atlas™ 995 Topographer (Carl Zeiss Meditec, Inc., Dublin, Ireland) and AccuPach V (Accutome, Malvern, PA, USA). The correlation between ORA parameters and various disease severity indices were examined using Pearson correlation coefficients and a stepwise logistic regression model.

Results: Patient Characteristics 93 eyes of 62 patients were included in the study. Patients were Caucasian (91%) or African-American (8%). Clinical diagnosis was keratoconus in 86 eyes (92.5%) and pellucid marginal degeneration n 7 eyes (7.5%). Patient Characteristics Mean ± SDUnits Age59.6 ± 10.8years Simulated K46.7 ± 4.4D Maximal topographic K 52.9 ± 6.1D CCT493 ± 64µm

Representative signals from keratoconic (KCN) eyes without scarring The waveform morphology and biomechanical parameters were correlated with the severity of keratoconus. Mild KCN Moderate KCN Severe KCN

Correlation of Central Corneal Thickness and Waveform Parameters There were significant correlations between central corneal thickness (CCT) and a number of ORA parameters including corneal hysteresis (CH), corneal resistance factor (CRF), Aindex, Bindex, W1, Aspect 1, Aspect11, Dslope 11, P1, and P2 (p<0.05). Width of peak 1 (W1) was found to be the most significant predictor of CCT (r=0.29, p=0.006). Plot of CCT and W1 (r=0.29, p=0.006) CCT W1

Correlation of Keratometry and Waveform Parameters Maximal topographic and steep simulated keratometries were significantly correlated with CH, CRF, inward applanation pressure (P1) and waveform score (WS) (see table). Flat and average simulated Ks were not significantly correlated with any ORA parameters (all p>0.05) ORA Waveform Parameters Maximal topographic Keratometry Steep simulated Keratometry rp valuer CH CRF-0.35< P WS-0.49<

Correlation of Waveform Parameters and Other Characteristics Corneal scarring also significantly altered waveform morphology and various parameters including CH, CRF, Aindex, Bindex, Aspect1, Aspect2, Uslope1, Uslope2, H1, H2, Dive1, Dive2, Mslew2, Slew2, Uslope21, Uslope11, Dslope21, H11, H21, W1, P1 and WS (p<0.05). Location of maximal corneal ectasia did not significantly affect ORA parameters. These parameters were not significantly different between keratoconus and pellucid marginal degeneration.

Conclusion We demonstrated that the corneal biomechanical parameters such as CH, CRF and also new ORA waveform parameter such as W1, and waveform score were significantly correlated to disease severity of ectatic corneas. These parameters might be helpful indicators to aid severity classification of keratoconus and pellucid marginal degeneration and monitor progression of the disease beyond the corneal thickness and corneal topography that have been used in the past.