Understand the Cornea Understand the Pressure Corneal Biomechanics, Accurate IOP, and CCT in one Simple Instrument.

Understand the CorneaUnderstand the Pressure Corneal Biomechanics, Accurate IOP, and CCT

in one Simple Instrument

•IOPG - Goldmann Correlated IOP•IOPCC - Corneal Compensated IOP•CH - Corneal Hysteresis•CRF - Corneal Resistance Factor•CCT - Central Corneal Thickness

One Device, Five Parameters

ORA Technology Background

Measuring “Pressure”Goldmann Tonometry Principles

The Goldmann Tonometer has long been considered the gold standard for measuring pressure. It is based upon the Imbert-Fick Law (W = P x A) where:

- W is the force to applanate- P is Intra Ocular Pressure (IOP)- A is the area applanated

Measuring “Pressure”Goldmann Tonometry Assumptions

- Surface is dry - Volume is perfectly spherical

- Surface is infinitely thin and perfectly flexible - Tear-film effect and corneal thickness effect cancel each other out

Recognizing that corneal effects and surface tension are factors which influence the measurement; Goldmann selected a tonometer tip size of 3.06mm which he believed would nullify these effects based on a constant central corneal thickness of 525 microns

Accordingly, Goldmann tonometry cannot compensate for differences in corneal thickness, corneal elasticity, and many other parameters that influence tonometer readings.

This applies to all other Goldmann-correlated tonometers!

- Experimentation done on cadaver eyes - Not representative of live corneas - Variation in corneal thickness is significantly greater than

assumed - Variations in corneal biomechanical properties unaccounted

Measuring “Pressure” Goldmann Tonometry Flaws

Non- Contact Tonometers

- Invented by Dr. Bernie Grolman in the 1960’s (American Optical)

- To enable OD’s in the USA to perform tonometry

- Introduced in 1971

- Uses rapid air pulse technology

- Easy to use

- Strong Goldmann correlation

- Objective: no operator bias

- No anesthetic required

- No risk of cross-contaminationModern NCT - AT555

NCT Traditional Method of Operation

“In conclusion, the current study shows that theXPERT vs GAT Sdiff (1.5 mmHg) is comparable tosingle GAT instrument repeatability, and far superiorto that of two GAT instrument repeatability/reliability.”

Traditional NCT vs. GAT

Ocular Response AnalyzerMethod of Operation

Static vs. Dynamic Measurement

Goldmann tonometers make ‘static’ measurements. That is they derive IOP from the force measured during a steady state applanation of the cornea.

The Ocular Response Analyzer makes a ‘dynamic’ measurement, monitoring the movement of the cornea in response to a rapid air impulse.

The ‘dynamic’ nature of the ORA measurement makes possible the capture of other useful data about the eye.

Visco-Elastic SystemAn Automotive “Strut” Assembly

- Coil Spring: Static Resistance (Elasticity). strain(deformation) is directly proportional to stress (applied force), independent of the length of time or the rate at which the force is applied.

- Shock Absorber: Viscous Resistance (Damping). The resistance to an applied force depends primarily on the speed at which the force is applied.

Method of Operation

Applanation Signal Plot

DefinitionsHysteresisThe phenomenon was identified, and the term coined, by Sir James Alfred Ewing in 1890.

Hysteresis is a property of physical systems that do not instantly follow the forces applied to them, but react slowly, or do not return completely to their original state.

Corneal Hysteresis

The difference in the inward and outward pressure values obtained during the dynamic bi-directional applanation process employed in the Ocular Response Analyzer, as a result of viscous damping in the cornea.

Corneal Hysteresis:A New Ocular Parameter

Right/Left Eye Hysteresis

R2 = 0.6625

0.00 5.00 10.00 15.00 20.00

R = 0.01

7 7.2 7.4 7.6 7.8 8 8.2 8.4Average Corneal Radius - mm

Hysteresis vs. Corneal Radius

R = 0.26

0 0.5 1 1.5 2 2.5 3

Corneal Astigmatism - D

Hysteresis vs. Corneal Astigmatism

CCT vs. CH - 184 normal eyes

Data courtesy Mitsugu Shimmyo, MD

Data courtesy New England College of Optometry

IOPG vs CH - 339 Normal Eyes

In/Out Applanation Regressions32 eyes - 3 pressure levels (ODM induced)

Conclusion: Hysteresis stays constant over a wide range of pressures for the same eyes

ORA and Corneal Specialties

Ocular Response Analyzer is the only instrument capable of measuring the biomechanical properties of the cornea.

Corneal Biomechanics:A New Area of Clinical Interest

Clinical data has shown that the Corneal Hysteresis measurement is useful in identifying corneal pathologies and may be valuable in identifying potential LASIK candidates who are at risk of developing ectasia. In consequence, the instrument is attracting interest from corneal specialists and refractive surgeons.

Corneal Biomechanics and Refractive Surgery

“Refractive surgery is not an exact science. Achieving the cornea’s ultimate shape depends on our ability to predict the biomechanical response to surgery.”Cynthia Roberts, Ph.D. Associate Professor of Ophthalmology and Biomechanical Engineering, OSU

“The promise of wavefront-guided laser ablation will not be fully realized until researchers gain a more complete understanding of corneal biomechanics.”John Marshall, Ph.D. “Father of the Excimer Laser”

“Wavefront by itself is a great tool but we still need to understand corneal biomechanics to reap the whole benefit.”David Williams, Ph.D. Direct of The Center For Visual Science, University of Rochester

Classifying Corneal Pathologies

Data courtesy Shah, Brandt, Pepose, Castellano

Classifying Corneal PathologiesTo investigate the biomechanical characteristics of eyes with:

- Fuchs’ Corneal Dystrophy (n=14)- Post-Penetrating Keratoplasty (18±10 months postop, n=32)- Corneal Ectasia (n=46)

- Advanced Keratoconus (CCT < 490 µm, n=15)- Pellucid Marginalis (n=4)- Early or Forme Fruste Keratoconus (CCT > 490 µm, n=27)

- Compared to 3 pachymetry matched control groupsGroup 1: > 580 µm (n=31)Group 2: between 510 and 580 µm (n=66)Group 3: < 510 µm (n=17)

To compare IOP measurements using 3 testing techniquesGAT; NCT with ORA; PDCT

Data courtesy Jay Pepose, MD - ASCRS 2006

Classifying Corneal PathologiesControl Group Differences

16.6 ± 2.717.5 ± 3.317.8 ± 2.3PDCT mmHg

12.8 ± 2.714.5 ± 3.215.3 ± 2.3GAT mmHg

13.2 ± 3.515.3 ± 3.117.6 ± 3.7ORA-g mmHg

15.0 ± 3.015.5 ± 3.215.5 ± 3.5ORA-cc mmHg

2.2 ± 0.9

7.8 ± 1.5

8.4 ± 1.2

487.9 ± 20.0

Group 3

2.3 ± 0.8

9.5 ± 1.3

9.7 ± 1.4

543.9 ± 18.3

Group 2

2.3 ± 1.1OPA mmHg

11.8 ± 1.8CRF mmHg

11.5 ± 1.8CH mmHg

603.7 ± 20.0CCT µm

Group 1

Controls

= p<0.05 comparing Group 1 or 3 to Group 2, with Student’s t-test

CH CRF OP

Biomechanical Metrics in 3 Control Groups

Group 1 (mean 603.8 µm) Group 2 (mean 543.9 µm) Group 3 (mean 487.9 µm)

2.2 ± 0.9

7.8 ± 1.5

8.4 ± 1.2

487.9 ± 20.0

2.2 ± 0.7

7.0 ± 1.8

8.1 ± 1.7

462.6 ± 77.4

KCN/PMD/

2.0 ± 0.9

5.6 ± 1.5

7.0 ± 1.4

400.9 ± 72.2

KCN advanced

2.3 ± 1.0

8.0 ± 2.0

585.3 ± 52.5

Fuchs’

2.3 ± 0.8

9.5 ± 1.3

9.7 ± 1.4

543.9 ± 18.3

2.6 ± 1.2

2.3 ± 1.1

9.2 ± 2.1

11.8 ± 1.8

9.2 ± 1.7

11.5 ± 1.8

533.0 ± 47.1

603.7 ± 20.0

CCTµm

PKPGroup

= p<0.05 comparing study group to its respective control group, with Student’s t-test

Thin Cornea with KeratoconusThin Cornea with no ectasia

CH=11.2CRF=10.8

CH=8.1CRF=7.9

Data courtesy Renato Ambrosio, MD - ASCRS 2006

NORMAL

3+ Corneal Gutata(Fuchs’Dystrophy)

CCT = 605 um; CH = 8.4mmHg; CRF = 8.0mmHg

CCT = 597 um; CH = 11.9mmHg; CRF = 11.4mmHg

Data courtesy Renato Ambrosio, MD - ASCRS 2006

Pre / Post Lasik

Data courtesy Dr. David Castellano, MD / Dr. Jay Pepose, MD

This patients pre-lasik CH is lower than the population average post-lasik CH. This patient may be a

candidate for ectasia!

Normal vs. Keratoconic Signals

NORMAL

KERATOCONUS

Data courtesy Mr. Sunil Shah, MD

NORMAL

Normal vs. Fuchs’ Signals

FUCHS’

Data courtesy Dr. James Brandt, MD

PRE-LASIK

POST-LASIK

Data courtesy Dr. David Castellano, MD

Pre and Post Lasik Signals

Signals are “Corneal Signature”

NORMAL KERATOCONUS

FUCHS’ POST LASIK

Predicting Ectasia Risk

Data courtesy Peter Hersh

ORA and Glaucoma

Landmark Studies

- OHTS - Ocular Hypertension Treatment Study

- AGIS - Advanced Glaucoma Intervention Study

- CNTGS - Collaborative Normal-Tension Glaucoma Study

- CIGTS - Collaborative Initial Glaucoma Treatment Study

Many of these studies have also investigated the role of the cornea in the diagnosis and management of glaucoma.

Many recent studies have concluded, for the first time, that controlling IOP in glaucoma patients and suspects stops or slows the progression of the disease. These studies include:

The cornea and glaucoma

• Some studies have investigated Corneal thickness as a contaminating factor in measuring IOP

• Others have investigated Corneal thickness as an independent indicator of glaucoma risk - Could a thin cornea be a surrogate for eyes susceptible to glaucoma damage?

Central Corneal Thickness

Recently a great deal of attention has been focused on the relationship between central corneal thickness (CCT) and Goldmann-obtained IOP values. Studies have found that corneal thickness influences the accuracy of IOP measurements.

- Thicker corneas, on average, tend to overstate GAT IOP values

- Thinner corneas, on average, tend to understate GAT IOP values

HOWEVER, this is only true ON AVERAGE for large populations

- The IOP/CCT relationship is actually quite weak and varies from study to study, making correcting IOP based on CCT impractical

Data courtesy New England Collage of Optometry

184 Normal Eyes

The problem with CCT

• Two corneas, both 0.65 mm

• One is clear

• The other is edematous

• The first reads high (compared to manometry), the second low

• Thickness can’t be the whole answer

• Other corneal factors besides thickness determine response of corneo-scleral shell to force

– Hydration

– Connective tissue composition

– Bio-elasticity

Data courtesy Harry Quigley, Wilmer Eye Institute

The problem with CCT

“Adjusting IOP by means of a fixed CCT algorithm is almost certainly wrong in the majority of our patients and is attempting to instill a degree of precision, into a relatively flawed instrument (the Goldmann tonometer), that simply is not there”

- James Brandt, Director of Glaucoma Services, UC Davis

“We should not assume that corneal thickness is the parameter of greatest interest in monitoring glaucoma or in determining what features of the eye are important in optic nerve damage”.

“Physiology is more important than anatomy” - Harry Quigley, Director of Glaucoma Service, Wilmer Eye Institute

CH distribution - Normals & Glaucoma

Data courtesy New England College of Optometry and Mitsugu Shimmyo, MD

Corneal Properties and Glaucoma Risk

Additional Parameters:

P1 and P2 provide independent information

about the eye

Background

Gaining additional Useful Information

•Clinical data analysis demonstrated that p1 and p2 respond independently to various factors (CCT, LASIK, IOP reduction, etc)

•Therefore, an “optimum combination” of the two independent parameters may yield the best IOP and Corneal Parameter, resulting in:

•Reduced or eliminated ORA IOP change after LASIK•Reduced or eliminated Corneal Parameter change after pressure reduction •Increased correlation of Corneal Parameter and CCT•Reduced or eliminated correlation of ORA IOP and CCT•Reduced or eliminated correlation of ORA IOP and Corneal Parameter•Reduced (slightly) correlation of ORA IOP and GAT•Higher correlation of Corneal Parameter with GAT than CCT with GAT•Reduced or eliminated anomalous low IOP for keratoconus, fuch’s patients

IOPccCorneal Compensated IOP

Define & Describe IOPCCCorneal-Compensated Intraocular Pressure

- An Intraocular Pressure measurement that is less affected by corneal properties than other methods of tonometery, such as Goldmann (GAT). IOPCC has essentially zero correlation with CCT in normal eyes and stays relatively constant post-LASIK.

- Developed using clinical data and a proprietary algorithm.

Method for finding “invariant” pressure

• Use linear combination of P1 & P2 - avoids potential coupling of IOP & CH

• Vary ratio of P1 & P2 to minimize difference of pre-post LASIK IOP

•Upon achieving desired post-LASIK results, verify that:•Correlation with Goldmann is still strong•Correlation of IOP with CCT in various data sets is minimal•Correlation of IOP with CH in various data sets is minimal

•Optimum formula: IOPcc = P2 - (0.43*P1)

IOPG vs. CCT - 184 normal eyes

Data courtesy New England Collage of Tonometry

IOPCC vs CCT 184 Normals

Data courtesy New England Collage of Optometry

IOPcc vs. GAT and DCT IOPThin, Average, and Thick Cornea Groups

GAT ORA-g ORA-cc PDCT

Group 1 (mean 603.8 µm) Group 2 (mean 543.9 µm) Group 3 (mean 487.9 µm)

28 eyes Pre/Post LASIK IOPCC

26% IOP drop 3% IOP drop

24 “NTG” eyes

Data courtesy Mitsugu Shimmyo, MD

IOPCC is higher than traditional IOP in “NTG” subjects

Is IOPcc Better than GAT?

•IOPcc correlates strongly with GAT on the average

•HOWEVER, IOPcc has the following advantages over GAT

•Not affected by CCT•Not affected by corneal biomechanical properties (rigidity)•As such, it is more accurate in KC, Fuchs’, OHT, NTG eyes•In addition, it has less measured IOP reduction post-LASIK•No operator bias

Is IOPcc Better than GAT?

CRFCorneal Resistance Factor

Define & Describe CRFCorneal Resistance Factor

An indicator of the overall “resistance” of the cornea, including both the viscous and elastic properties. It is significantly correlated with Central Corneal Thickness (CCT) and GAT, as one might expect, but not with IOPCC.

Method for finding “CRF”corneal resistance factor

• Use linear combination of P1 & P2 - avoids potential coupling of IOP & CH

• Vary ratio of P1 & P2 to:•Maximize correlation of CH and CCT in various populations•Minimize CH change after pressure reduction / increase•Maximize correlation of CH and GAT•Ensure CH remains significate indicator of corneal conditions such as Keratoconus, fuch’s, etc•Ensure significant CH change post-LASIK remains

•Optimum corneal parameter: CRF = P1-(0.7*P2)

Correlation of CRF and CCT

Correlation of CH and CRF vs. CCT339 Normal Eyes

Correlation of CH & CRF vs. IOPG (“GAT”)

CRF - Normals, Keratoconus, Fuchs’

Data courtesy Shah, Brandt, Pepose, Castellano

CRF is a better indicator of KC than CH

CRF distribution - Normals & Glaucoma

Data courtesy New England College of Optometry and Mitsugu Shimmyo, MD

How do CH and CRF DifferCorrelation of CH, CRF & IOPg

Data courtesy Dr. Mitsugu Shimmyo, MD

IOPCC vs CRF 339 Normals

Are CH and CRF Related tothe “Modulus of Elasticity”?

Researchers have attempted to identify the young's modulus of the cornea - but the reported values in the literature, vary by four orders of magnitude!

The cornea is a system, not an isotropic material such as steel or rubber. Attempting to identify the youngs modulus is a gross over-simplification of a complex subject.

Interpreting ORAMeasurement Results

Measurement Signal Components

Air Pulse

Raw Signal

Filtered Signal

Applanation Events

IOPg IOPcc CH CRF CCTHighAveLow

Identifying Normal Signals“Rules of thumb”

- Watch for:

- Clean, smooth signals

- Similar amplitude peaks

- Repeatable values

- Consistent measurements in both eyes

X X X X X

Identifying Normal SignalsIOPcc and IOPg are close and in normal range

CH and CRF are close and in normal range

Baseline signal is “flat” and nearly same amplitude on both sides

Raw signal is fairly smooth

Raw signal has clean points

Filtered peaks “line up” under raw peaksSimilar signal amplitude

Identifying Normal Signals

Identifying Keratoconus“Rules of thumb”

- Watch for:

- Low amplitude peaks

- less repeatable signals than normal subject

- “noisy” signals

- Often present in one eye and not the other.

X XX X XX

Identifying Keratoconus Signals

Low CHLow CRF

IOPcc Higher than IOPG

Thin CCTLow amplitude peaks

Sharp, thin peaks

P2 raw signal “bounce”

More “noisy” raw signal Noisy signals cause less repeatable values

Identifying Keratoconus Signals

Questionable Keratoconus SignalMeasurement may yield unreliable results

Raw signal is too “lumpy”

Identifying Severe Keratoconus“Rules of Thumb”

- Look at the signal, the numbers may be unreliable

- Thin CCT

- Very low amplitude peaks - practically a flat line

- General signal shape is very repeatable

- Often present in one eye and not the other

???????????

Severe Keratoconus SignalMeasurement values will be unreliable

CH and CRF are unreliable

due to signal amplitude

Forget about the CH, no question this Keratocouns!!

Identifying Forme Fruste KC“Rules of Thumb”

- Watch for:

- Rule out past history of refractive surgery

- lower amplitude peaks

- Rapid P2 raw signal falloff with small “ricochet bounce”

- Suspicious topography

- “noisy” signals, but cleaner than advanced KC and more repeatable

- Family history, frequent eye-rubbing, trouble wearing contacts

XX X X XX

“Sub-Clinical” Keratoconus SignalSignal looks nearly normal but low CH and CRF

CH just below normal rangeCRF just below normal range

Mild P2 raw signal “bounce”

Identifying Refractive Surgey“Rules of Thumb”

- Watch for:

- low amplitude peaks (cleaner in LASIK than PRK)

- “Sharp / thin” raw signals (especially in LASIK)

- Rapid P2 raw signal falloff with pronounced “ricochet bounce”

- less repeatable signals than normal subject (Especially in PRK)

- “noisy” signals (Especially in PRK)

X XX X XX

Pre / Post-LASIK SignalsPRE-LASIK

POST-LASIKNormal Signal

IOPg, IOPcc close and in normal range

Reduced signal amplitude

Thin, sharp peaks

P2 “bounce”

Some “noise”

CH, CRF close and in normal range

IOPcc higher than IOPg, closer to normal

CH, CRF low

CCT lower

Pre / Post-LASIK Signals PRE-LASIK

POST-LASIK

Pre / Post-LASIK SignalsExample of less reliable, but still useful, signals

PRE-LASIK

POST-LASIK

P1, not ideal

CH, CRF may be higher in reality

P1, not ideal

CH may be lower in realityBut the CRF is reduced!

IOP probably higher in reality

Neither signal is “ideal” but thepost-lasik difference is still clear.

TAKE MULTIPLE READINGS!!

PRE-PRK

Pre / Post PRK Signals

Normal Signal

2 wks POST-PRK

IOPg, IOPcc close and in normal rangeCH, CRF close and in normal range

CH, CRF reduced PRK signals are noisy

2 Months POST-PRK

Signal improves with time

But CH, CRF stay low

Note how well IOPcc works!

Identifying Ectasia“Rules of Thumb”

- Watch for:

- Has had LASIK, PRK, other surface ablation procedure

- Very low amplitude, noisy, “messy” signals

- Signal quality does not improve over time

- Suspicious topography

- Often present in one eye and not the other

X X XX

Identifying Ectasia Signals

Low CHLow CRF

Thin CCT

Low amplitude peaksSharp, thin peaks

P2 raw signal “bounce”

Lots of noise

Identifying POAG“Rules of Thumb”

- Watch for:

- IOPcc higher than IOPg

- Noisy signals

- Family history, race, age, CDR, Diabetes status, Visual fields results, optic nerve status

XX X X

Identifying POAG SignalsUncontrolled Subject, moderately high IOP

Low CHCRF higher than CH

IOPg, IOPcc both elevatedSignals are high amplitude, noisy

Identifying POAG SignalsSubject on meds, but progressing

Low CHLow CRF

IOP is in normal rangebut IOPcc Higher than IOPG

Signal is smoother

than high IOP signals

Identifying POAG SignalsSubject on meds and stable

CH, CRF in normal range

IOP is well controlled

Signal is smooth

Identifying POAG SignalsUncontrolled Subject - Blind

Low CHHigh CRF

IOPg, IOPcc both elevated

Signals are low amplitude, lumpy, and noisy

Identifying OHT“Rules of Thumb”

- Watch for:

- IOPcc lower than IOPg

- Smooth signal

XX X XX

Identifying OHT SignalsSubject is a “false positive”

CH, CRF are very highIOPg much higher than IOPcc

Signal is smooth

Rules-of-thumbSpotting NTG/LTG

- Watch for:

- IOPcc higher than IOPg, but may still be in “normal” range

- Low amplitude signals, some noise

XX X X

Identifying NTG Signals

Low CHLow CRF

Thin CCTLow amplitude peaks

Rules-of-thumbSpotting “unusual” eyes / corneas

- Atypical measurement signals that are:

- less repeatable than normal

- highly variable numeric measurement values

- Investigate previous ocular history for surgery, disease, trauma, etc

- What to do:

- take a series of measurement

- look for the “best signals” possible

- try to get two that look similar and yield similar results

- delete clearly “bad” signals and use average values of good ones

Unusual Signals

“Bizarre” signals are often very repeatable

Just the fact that they are “different” is telling us something about the cornea / eye

Understand the Cornea Understand the Pressure Corneal Biomechanics, Accurate IOP, and CCT in one Simple Instrument.

corneal effects

corneal elasticity

pressure corneal biomechanics

corneal thickness effect

measurement goldmann

applied force

parametersiopg goldmann

goldmanncorrelated tonometers

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