Ocular Response Analyzer Waveform Analysis in the Ectatic Corneas:

Correlation of the New Corneal Biomechanics Parameters and Severity of

KeratoconusTeeravee Hongyok, MD, Elisabeth J. Cohen, MD, Kristin M. Kristin M.

Hammersmith, MD, Peter R. Laibson, MD, Christopher J. Rapuano, MDHammersmith, MD, Peter R. Laibson, MD, Christopher J. Rapuano, MD

Cornea Service, Wills Eye InstituteJefferson 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):156-62.2 Kirwan C, et. al. Ophthalmologica 2008;222(5):334-7.3 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 Name Description

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

P1area P1area1 area under the curve of peak1 (sum of values)

P2area P2area1 area under the curve of peak2 (sum of values)

Aspect1 Aspect11 aspect ratio (height/width) of peak1

Aspect2 Aspect21 aspect ratio (height/width) of peak2

Uslope1 Uslope11 rate 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) ***

Dslope1 Dslope11 rate 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) ***

W1 W11 width of peak1 at "base" of peak1 region

W2 W21 width of peak2 at "base" of peak2 region

Parameter Name Description

From 75% of Applanation Peak*

From 50% of Applanation Peak**

H1 H11 height (from lowest to highest value) of peak1

H2 H21 height (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

Path1 Path11 absolute value of path length around peak1

Path2 Path21 absolute 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. 2009 Dec;107:282-99.)

• 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 2.04.

• 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 ± SD Units

Age 59.6 ± 10.8 years

Simulated K 46.7 ± 4.4 D

Maximal topographic K

52.9 ± 6.1 D

CCT 493 ± 64 µm

Location of maximal corneal protrusion

35%

23%

19%

17%

4%

2%

Infero-centralInfero-temporalInferiorCentralTemporalInfero-nasal

Refractive Correction

80%

8%

8%2%2%

RGPHybrid CLSpectaclesSoft CLNone

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

r p value r p valueCH -0.32 0.002 -0.27 0.021

CRF -0.35 <0.001 -0.33 0.004

P1 -0.28 0.008 -0.29 0.013WS -0.49 < 0.01 -0.37 0.001

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.