understand the cornea understand the pressure corneal biomechanics, accurate iop, and cct in one...
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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
for
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
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R = 0.01
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7 7.2 7.4 7.6 7.8 8 8.2 8.4Average Corneal Radius - mm
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Hysteresis vs. Corneal Radius
R = 0.26
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Corneal Astigmatism - D
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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
31
Group 3
2.3 ± 0.8
9.5 ± 1.3
9.7 ± 1.4
543.9 ± 18.3
66
Group 2
2.3 ± 1.1OPA mmHg
11.8 ± 1.8CRF mmHg
11.5 ± 1.8CH mmHg
603.7 ± 20.0CCT µm
17N
Group 1
Data courtesy Jay Pepose, MD - ASCRS 2006
Controls
= p<0.05 comparing Group 1 or 3 to Group 2, with Student’s t-test
Classifying Corneal Pathologies
Data courtesy Jay Pepose, MD - ASCRS 2006
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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)
Classifying Corneal Pathologies
2.2 ± 0.9
7.8 ± 1.5
8.4 ± 1.2
487.9 ± 20.0
31
Group
3
2.2 ± 0.7
7.0 ± 1.8
8.1 ± 1.7
462.6 ± 77.4
46
KCN/PMD/
FFKCN
2.0 ± 0.9
5.6 ± 1.5
7.0 ± 1.4
400.9 ± 72.2
15
KCN advanced
2.3 ± 1.0
8.0 ± 2.0
8.0 ± 2.0
585.3 ± 52.5
14
Fuchs’
2.3 ± 0.8
9.5 ± 1.3
9.7 ± 1.4
543.9 ± 18.3
66
Group
2
2.6 ± 1.2
2.3 ± 1.1
OPA
9.2 ± 2.1
11.8 ± 1.8
CRF
9.2 ± 1.7
11.5 ± 1.8
CH
533.0 ± 47.1
603.7 ± 20.0
CCTµm
3217N
PKPGroup
1
Data courtesy Jay Pepose, MD - ASCRS 2006
= 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
Classifying Corneal Pathologies
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
Classifying Corneal Pathologies
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
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
Background
Data courtesy Dr. David Castellano, MD / Dr. Jay Pepose, MD
Background
Data courtesy Dr. David Castellano, MD / Dr. Jay Pepose, MD
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
Data courtesy Jay Pepose, MD - ASCRS 2006
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GAT ORA-g ORA-cc PDCT
Group 1 (mean 603.8 µm) Group 2 (mean 543.9 µm) Group 3 (mean 487.9 µm)
Data courtesy Dr. David Castellano, MD / Dr. Jay Pepose, MD
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”?
NO!
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
P1
Applanation Events
P2
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 Normal Signals
Identifying Normal Signals
IOPg IOPcc CH CRF CCTHighAveLow
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
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
IOPg IOPcc CH CRF CCTHighAveLow
???????????
Severe Keratoconus SignalMeasurement values will be unreliable
CH and CRF are unreliable
due to signal amplitude
Forget about the CH, no question this Keratocouns!!
IOPg IOPcc CH CRF CCTHighAveLow
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
IOPcc Higher than IOPG
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)
IOPg IOPcc CH CRF CCTHighAveLow
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
IOPg IOPcc CH CRF CCTHighAveLow
X
X X XX
Identifying Ectasia Signals
Low CHLow CRF
IOPcc Higher than IOPG
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
IOPg IOPcc CH CRF CCTHighAveLow
XX X X
XX X
XX 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
- Family history, race, age, CDR, Diabetes status, Visual fields results, optic nerve status
IOPg IOPcc CH CRF CCTHighAveLow
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
- Family history, race, age, CDR, Diabetes status, Visual fields results, optic nerve status
IOPg IOPcc CH CRF CCTHighAveLow
XX X X
XX
X
Identifying NTG Signals
Low CHLow CRF
IOPcc Higher than IOPG
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