CORNEAL HYSTERESIS

• The cornea can be defined by its physical dimensions, such as thickness, or by the physical behavior in the form of biomechanics.

• Corneal biomechanics may play an important role in the accurate measurement of intraocular pressure (IOP).

• Given the cornea’s continuity with the lamina cribrosa, corneal biomechanics can be regarded as a surrogate for the overall globe biomechanics. It can therefore, indicate the susceptibility of the optic nerve head to damage from elevated IOP.

• Whereas corneal thickness is a static physical property, corneal biomechanics refers to the dynamic behavior of the cornea.

• Elasticity and Viscosity:

·         Both elasticity and viscosity are mechanical properties that describe how a material deforms (“strain”) in response to an external load (“stress”).

·         An elastic material, such as a spring, regains its original position by following the exact pathway of its initial displacement after removal of the external force. The slope of the stress-strain plot defines the elasticity modulus, or Young’s modulus, of a material.

·         Conversely, a viscous material does not follow the exact path of deformation to regain its original shape upon removal of the stress.

• The cornea exhibits both elastic and viscous properties that can be explained by the two constituents of its stroma: collagen fibers and the ground substance. Collagen fibers are the main load-bearing substance and provide elasticity whereas the ground substance, composed of glycosaminoglycans (GAGs) and proteoglycans (PGs), offers viscosity.

• When attempting to measure corneal biomechanical properties, it is important to note that the cornea is a dynamic, viscoelastic, and structurally heterogeneous material. Therefore, any measurement of corneal biomechanics will be affected by the amount and the rate at which the stress is applied, the location of the cornea where the measurement is made, the IOP, as well as the age.

• Hysteresis, from Greek meaning “lagging behind”, is the difference between how a material deforms and reforms during loading and unloading from an applied force. It is a property of materials that combine elasticity and viscosity.

• The corneal stroma consisting of GAGs and PGs is viscoelastic and has hysteresis. This allows the cornea to absorb and dissipate energy during a stress-strain cycle when a force is applied.

• Corneal hysteresis (CH) is not an inherent property of the cornea, but rather reflects how the cornea reacts to an external force. CH reflects the viscous damping ability of the cornea provided by GAGs and PGs within it.

• The average CH in normal eyes has been shown to range from 9.6 to 10.7 mmHg with strong correlation between the two eyes of the same patient.

• Several cross sectional studies have shown corneal hysteresis (CH) to be lower in eyes with primary open angle glaucoma (POAG) compared to normal eyes, with mean CH values in POAG ranging from 8 to 10 mmHg. Similarly, CH has also been shown to be lower in normal tension glaucoma (NTG) when compared to normal eyes, but higher in NTG than POAG eyes. Based on different studies, the difference in CH between POAG and normal eyes can range between 1 to 2 mmHg. It has also been reported that CH values can discriminate between normal, POAG, and ocular hypertensive/glaucoma suspect eyes. In addition, CH was recently shown to decline at a faster rate in POAG compared to normal eyes.

• CH was also found to be lower than normal in angle closure glaucoma, pseudoexfoliative glaucoma and congenital glaucoma.

• CCT is almost always very similar, if not identical, between the two eyes; it doesn’t change very much based on the IOP. In contrast, hysteresis will often vary, and it does vary with a change in IOP.

• Higher CH, but not CCT, has been shown to correlate with more optic nerve surface compliance during artificially induced IOP elevations in the eyes of glaucoma patients. This suggests that eyes with higher CH may be better able to tolerate IOP spikes. Conversely, CH is significantly lower in POAG patients with acquired pit of the optic nerve – a change indicative of glaucomatous damage – than those who do not have such changes. Other structural markers of the optic nerve such as cup-to-disc ratio and Heidelberg Retina Tomograph (HRT) rim area are also associated with CH.

• Low CH was associated with greater mean cup depth and larger cup-to-disc ratio, independent of IOP and disc size. (Conversely, low CCT was only associated with mean cup depth).

• The data suggests that CH may either directly contribute to the pathogenesis of optic nerve damage in glaucoma or may serve as a surrogate marker for overall globe biomechanics. A definitive link between CH and ONH damage, however, is not yet established, with other studies showing no correlation between CH and RNFL thickness or cup-to-disc ratio.

• CH has also been shown to be associated with functional changes in glaucoma. Congdon et al. were the first to show that low CH, but not CCT, was associated with progressive visual field loss in glaucoma patients over 5 years. Medeiros et al recently demonstrated in a prospective study that for each 1 mmHg decrease in baseline CH, there was 0.25% faster rate of visual field index decline over time in glaucoma patients. 

• In POAG patients with asymmetric visual fields, the worse eye had lower CH.

• De Moraes has also shown that low CH is associated with faster rates of glaucoma progression.

• It has been reported that in healthy patients, there is a strong positive correlation between CH and CCT. By comparison, there is a positive, but much weaker correlation between CH and CCT in glaucoma patients.

• Low baseline CH (and not CCT) was associated with greater IOP reduction. Lower CH was shown to result in a higher IOP lowering response in patients being treated with topical prostaglandin analogs, selective laser trabeculoplasty, tube shunts, as well as trabeculectomy.

• IOP is negatively correlated with CH such that the higher the IOP, the lower the CH. 

• La Place’s law, which states that wall tension is a function of internal pressure, can help understand this concept. As IOP increases, the cornea becomes stiffer and its damping ability reduces. It is therefore important to account for CCT and IOP to isolate the effect of CH, both in clinical settings as well as in research studies.

• Viscous substances responsible for CH decrease with age resulting in lowering of CH over time. The rate of CH decline over time has been estimated to range from 0.24 to 0.7 mmHg/decade in normal eyes.

• CH shows inter-individual variability. It is not strongly correlated with other common metrics such as corneal radius, astigmatism, spherical equivalence, axial length and IOP measured on Goldmann Tonometry. CH is lower in patients with corneal disorders such as Fuch’s disease and keratoconus. 
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• The in vivo measurement of corneal biomechanics was first made possible in 2005 with the advent of the Ocular Response Analyzer (ORA). 

• https://ourgsc.blogspot.com/search?q=tonometer 

• The ORA is based on bi-directional noncontact applanation pneumotonometry. In this scenario, corneal hysteresis reflects the ability of corneal tissue to absorb and dissipate energy during a bidirectional applanation process.

• An accelerating air pulse is generated by the ORA to slightly indent the cornea. As the cornea moves inwards and outwards in response to the increasing and decreasing velocity of the air jet, its deformation is tracked by an electro-optical system. The inward and outward applanation events are identified by the peak amplitude of the reflected light hitting the photodetector.

• Two pressure measurements, P1 and P2, are recorded within 20 milliseconds using the electro-optical system. The pressure values at the inward (P1) and outward (P2) applanation states are a function of the IOP, static resistance of the cornea and the dynamic (viscous) resistance of the cornea.

• The average [(P1+P2)/2] and the difference (P1-P2) of these two measurements are recorded as Goldman-correlated IOP (IOPg) and corneal hysteresis (CH), respectively.

• Two other parameters obtained during an ORA measurement are corneal-compensated IOP (IOPcc) and corneal resistance factor (CRF). IOPcc is derived from an algorithm based on pre- and post-LASIK data and is considered to be less affected by the cornea. CRF is a measure of the cornea’s overall resistance related to elastic properties of the cornea and is not associated with CH. The precise meaning and application of IOPcc and CRF is not completely understood.

• The ORA software generates a reliability indicator called “waveform score” for each measurement. This should be taken into account when interpreting ORA data, with a waveform score of <3.5 suggesting an unreliable measurement.

• Race, gender, axial length, spherical equivalent, and myopia have no significant effects on ORA measurements.

• A normal tear film is important for a proper reflected light signal and accurate ORA measurement.