The risks of being hysterical

Recent times have seen a shift in consciousness for the glaucomatologist. Today, when evaluating a patient’s risk of developing glaucoma, no longer is the focus solely on their optic nerve head (ONH) or intraocular pressure (IOP) measurement. Now, during the clinical work-up, it seems the cornea is routinely the centre of attention. This is most likely due to the results of the United States Ocular Hypertension Treatment Study (OHTS), which in 2002 reported that central corneal thickness (CCT) was an important predictive risk factor for the development of primary open angle glaucoma (POAG). The exact role of the cornea in the development of POAG has been the subject of great interest and debate. Do corneal effects simply concern IOP measurement accuracy, or are corneal properties a reflection of the structural characteristics of the posterior peripapillary sclera and ONH? Studies have shown that differences in CCT alone cannot account for all of the variation in measured IOP among individuals, and other more complex corneal biomechanical properties have an important influence on IOP measurement. Studies have also shown that although there is no relationship between CCT and anterior or peripapillary scleral thickness, there is an inverse relationship between CCT and ONH area. Thus, eyes with thinner corneas may have larger, and consequently more deformable, optic discs, making them more prone to pressure-induced damage. But the evidence also suggests that CCT does not tell us the whole story and is only a surrogate measure of corneal biomechanics. Until recently, corneal material properties could only be studied ex vivo using button inflation or strip extensiometry testing techniques. The introduction of the Reichert Ocular Response Analyzer (ORA; Reichert Inc., Buffalo, NY, USA) in 2005 changed the scene. The ORA measures the dynamic corneal response to a jet of air. A metered air-pulse is directed at the cornea until the cornea applanates. This applanation event acts as a trigger to terminate the air-pulse following a slight further increase in air pressure which causes a corneal indentation. At this point, the air pressure steadily reduces until it is completely removed. The instrument makes two measurements – the force required to flatten the cornea as the air pressure rises (‘force-in’ applanation) and the force at which the cornea flattens again as the air pressure reduces (‘force-out’ applanation). It has been found that the second ‘force-out’ applanation occurs at a lower air pressure than the first ‘force-in’ applanation, and this has been attributed to the dampening effects of the cornea. The difference between the two pressures has been termed ‘corneal hysteresis’ (CH). The ORA has a number of advantages; being a non-contact device, it is extremely easy to operate and provides a rapid measure of corneal properties. This potentially makes it an excellent screening device that could be readily utilized in clinical practice. Furthermore, as CH is a direct, in vivo, measure of corneal biomechanical properties, this has opened up the real possibility of relating corneal properties to those of the sclera at the posterior pole. But what exactly is it describing? The term CH is often erroneously interchanged with corneal ‘stiffness’ or ‘elasticity’, but CH describes the viscous dampening properties of the cornea. These properties are dependent on a number of other variables, including the degree of air pressure applied and the actual IOP of the eye under investigation. CH has been shown to decrease with age, increase with increasing CCT, reduce following refractive surgery procedures, and be altered in corneal dystrophies. But can it be used as a marker of scleral properties at the posterior pole? In this month’s issue of Clinical and Experimental Ophthalmology, Shah and associates present the results of a cross-sectional, hospitalbased study comparing CH in eyes with ocular hypertension (OHT), ‘normal’ tension glaucoma (NTG) and POAG. The study found that CH was lowest in eyes diagnosed with NTG and highest in those with OHT. The authors suggest that CH may be more useful than CCT when attempting to assess the accuracy of IOP measurements. In another hospital-based study by Congdon et al, low CH was found to be a predictor of visual field progression. The inference from these studies is that low CH could be indicative of a structural weakness within the posterior peripapillary scleral region that could make eyes more prone to IOP-induced damage. However, as with all hospital-based studies, case selection is often cited as a source of bias and, as such, the results of this type of study are usually interpreted with caution. An attempt to assess the nature of CH on ONH compliance has recently been attempted by Wells et al. In their rather elegant study, ONH imaging was performed prior to and during IOP elevation in 100 subjects, comprising those diagnosed with glaucoma and similar-aged control subjects. ONH compliance was measured as a change in the optic cup depth during the IOP elevation period. In glaucoma patients, CH was significantly positively associated with change in optic cup depth. A low CH suggests a reduction in the viscous dampening properties of the cornea, which in turn suggests a stiffer structure. Well’s study showed that glaucoma patients with low CH exhibited less ONH compliance (as measured by change in optic cup depth) compared with those with greater CH. This lends support to the speculation that low CH may indicate increased stiffness not just of the cornea, but also the ONH. That changes were only seen in glaucoma patients also supports the idea that the biomechanics of the peripapillary sclera and ONH are altered in the condition, such that these tissues behave differently in those with the disease than in those without it. Whether having a low CH suggests a predisposition for POAG or whether it simply reflects a change caused by the condition is yet to be elucidated. Further research is, as always, required. In the meantime, it appears that not being hysterical may not be such a good thing after all. Clinical and Experimental Ophthalmology 2008; 36: 499–500 doi: 10.1111/j.1442-9071.2008. 01842.x