KEY CONCEPTS
Diagnosis, refractive screening, and collagen cross-linking changes in keratoconus with:
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Ocular Response Analyzer (ORA) and Corvis ST
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Brillouin microscopy
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Ex vivo assessment of corneal biomechanics.
Background
Since 1854, when John Nottingham published the first detailed description of keratoconus (KC), 1 corneal diagnostic devices have been evolving. In 1880 Placido developed the first keratoscope based on corneal reflections of a series of concentric rings. In 1980 Klyce refined this technology and introduced computerized videokeratoscopy, allowing for better evaluation of the anterior corneal curvature and improving KC detection. In the 1990s, with the proliferation of refractive surgery, the need for better screening for KC increased. This became yet more relevant in 1998 when the first case of iatrogenic ectasia was reported in a patient with forme fruste keratoconus (FFKC). Reports of postrefractive surgery ectasia steadily increased. Fortunately, advances in KC diagnostic imaging methods also continued.
Currently, the anterior and posterior corneal surfaces of the cornea can be evaluated with corneal tomography, and pachymetric distribution patterns can be assessed with anterior segment optical coherence tomography (AS-OCT). In addition, confocal microscopy and wavefront analysis have resulted in a greater capacity to evaluate corneal characteristics such as structural alterations and corneal aberrations. However, current options for evaluating corneal biomechanics—properties of the cornea that have been demonstrated to play an important role in KC—are limited.
Biomechanics
In the field of biomechanics the micro and macro effects of forces acting on living organisms are studied. Our understanding of the biomechanical features of human tissues has contributed to improving understanding of diseases and has enhanced the prediction of tissue alterations. To comprehend the biomechanical response of living tissues, two concepts are fundamental: Young’s modulus and viscoelasticity ( Box 20.1 ).
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Young’s Modulus (Elastic Modulus). Describes the stiffness of a material. The higher the modulus, the more rigid the material is and more difficult it is to deform.
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Viscoelasticity. Intrinsic characteristic of a living tissue, partially characterized by hysteresis. It describes the capability of a material to return to its prestress configuration and is dependent on the strain.
In Vivo Assessment of Corneal Biomechanics
OCULAR RESPONSE ANALYZER
In 2005 Reichert Technologies launched the first device for in vivo evaluation of corneal biomechanics. , The device, named Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Depew, NY), works by emitting an air-pulse in the central 3 mm of the cornea capable of producing an inward deformation of the tissue. When the first applanation moment is detected (also called first state of applanation), the air-pulse signal is terminated. However, the inertia of the air pulse continues to raise the air pressure, and the cornea reaches a concavity configuration peak. Subsequently, the air pressure diminishes allowing the cornea to gradually return to its original configuration. During the outgoing phase, a second moment of applanation (or second state of applanation) is also detected ( Fig. 20.1 ). An infrared emitter detects the two states of applanation and measures the emitted air pressure at those moments (see P1 and P2) (see Fig. 20.1 ). , From these measurements, the ORA software obtains several important corneal biomechanical parameters ( Box 20.2 ).
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Corneal Hysteresis (CH) . Difference between P1 and P2 (P1 − P2, see Fig. 20.1 ).
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Corneal Resistance Factor (CRF) . Equals P1 – kP2, where k (0.7) is a manufacturer constant to enhance the dependence on central corneal thickness (see Fig. 20.1 ).
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Hysteresis Loop Area (HLA) . Area enclosed by pressure versus applanation function.
ORA in Keratoconus
( Table 20.1 )
| Parameter | Normal | Keratoconus | Sensitivity | Specificity | ||
|---|---|---|---|---|---|---|
| CH (mmHg) | >8.50 | ≤8.50 | 52% | 95.4% | ||
| CRF (mmHg) | >8.60 | ≤8.60 | 77.6% | 86% | ||
| HLA | >92.629 | ≤92.629 | 88.8% | 88.9% |
Studies have shown a significant decrease in both corneal hysteresis (CH) and corneal resistance factor (CRF). , However, ORA has poor sensitivity and specificity for detecting mild KC ( Fig. 20.2 ). ,
ORA in Refractive Surgery
After refractive surgery, a decrease in CH and CRF has been reported. , This effect is more pronounced after LASIK surgery than with photorefractive keratectomy (PRK).
ORA in Cross-Linking
No changes in CH and CRF have been detected after collagen cross-linking (CXL) for KC.
ORA Limitations
According to some studies, there is an unclear relationship between corneal mechanical properties, such as Young’s modulus, and CH and CRF, as well as an overlap between elasticity and viscosity. These circumstances make data difficult to interpret. , Moreover, the new ORA software provides 42 new variables; however, more studies are needed to determine their clinical significance. Also, air-puff pressure is not constant, making measurements difficult to compare between eyes.
CORVIS ST
In 2009 Oculus introduced the Corvis ST noncontact tonometer (OCULUS Optikgeräte GmbH, Wetzlar, Germany) for biomechanical evaluation of the cornea. This device combines dynamic applanation with an ultra-high-speed Scheimpflug camera (4330 frames/second) that records an 8-mm wide horizontal section of the cornea ( Fig. 20.3 ). , , The air emitted by the noncontact tonometer does not vary from one measurement to another and the corneal response, recorded by the Scheimpflug camera, is analyzed to obtain the corneal biomechanical variables ( Box 20.3 ).
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Deformation Amplitude (DA) . Maximum inward movement of the corneal apex.
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First Applanation . Event that occurs during the first flattening of the cornea during the air puff (in milliseconds). The length of the applanation at this moment is measured in millimeters.
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Second Applanation . Event that occurs during the second flattening of the cornea during the air puff (in milliseconds). The length of the applanation at this moment is measured in millimeters.
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Corneal Velocities (CVel). Maximum velocities in ingoing and outgoing phases. Expressed in meters per second.
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Highest Concavity . The length distance between the two peaks (in millimeters) during the air puff (in milliseconds).
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Ambrósio Relational Thickness Over the Horizontal Meridian (ARTh) . Index that represents the characterization of the thickness data on the horizontal Scheimpflug image.
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Corvis Biomechanical Index (CBI) . Index based on combining ARTh with 16 dynamic corneal response (DCR) parameters.
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Tomographical/Biomechanical Index (TBI) . Index that combines tomographic and biomechanical data. ,
Corvis ST in Keratoconus
( Table 20.2 )
Studies have found higher deformation amplitude (DA) values in KC patients; however, this parameter cannot differentiate between healthy and KC corneas (due to its low sensitivity and specificity). ,
Both the Corvis biomechanical index (CBI) with a 0.5 cutoff and the tomographical/biomechanical index (TBI) with a 0.79 cutoff demonstrated high sensitivity and specificity for KC detection (100% sensitivity with 94.1% specificity and 100% of sensitivity with 100% specificity, respectively). , ,
In Fig. 20.4 , the Ambrósio, Roberts, Vinciguerra (ARV) Corvis ST display of a patient with a very asymmetric ectasia (normal tomography in the right eye [VAE-NT], and ectasia in the left eye [VAE-E]) is shown. The display shows abnormalities in the tomographic assessment, the CBI index, the TBI index, and the Belin/Ambrósio deviation index (BAD-D, Box 20.4 ).
