In our study, the populations of case and control eyes were comparable in age, but the sex ratio was different between both groups. The cases were predominantly male, the sex ratio being 1.94 (male to female) in the whole keratoconus database. To our knowledge, however, in the literature, there is no reported difference in viscoelastic properties in vitro or in ORA values between men and women. Therefore, this difference probably did not influence the results of the study.
22–24,26–30
In published research, keratectasia after LASIK has been shown to occur after a mean follow-up of 14 and 16 months.
6,7 To select eyes with a low probability of presenting with a corneal biomechanical instability, the control eyes came from the preoperative database of patients undergoing LASIK with a follow-up of more than 24 months. In this group, the mean values of CH and CRF were close to published data for the whole population.
22–24,26,27
Keratoconus is a progressive, bilateral, and asymmetric corneal dystrophy.
12,31,32 Hence, we expect the normal eye of patients with unilateral expression of keratoconus to present with a latent biomechanical instability, which we define as a forme fruste of keratoconus. Topographic KISA scores to screen keratoconus were very low in our case group. Rabinowitz and Rasheed
20 considered a KISA score between 60% and 100% as FFKc and a score less than 60% as normal.
Although the CCT measurements with US pachymetry is less variable, we chose Orbscan II slit lamp biomicroscopy to allow a good repeatability and reproducibility of measured values with an acoustic factor of 0.92 and to ensure low intra- and interobserver variations.
33–36 In published data, CH and CRF had a positive and moderate correlation with CCT, but were no measurements of the same biomechanical parameters.
21–26 We found similar moderate correlation coefficients with CCT in our study. Hence, we chose to match our case and control eyes in four groups of similar CCT to eliminate the difference of 23 μm in the mean CCT of cases and controls that could influence CH and CRF mean values of the study, to improve the sensitivity of ORA values, and to reduce the influence of CCT on measured parameters. We determined the size of each CCT group so that it provided a sufficient number of cases and control eyes for statistical analysis. Control and case eyes matched in four groups of CCT had similar mean values, and value-scattering was homogeneous.
CH was different between the cases and controls in each CCT group, but CRF seemed to be a better parameter for screening FFKc, with a significant difference of 1.1 to 2.2 mm Hg between the cases and controls, CH having smaller differences. This confirms the different viscoelastic behavior of corneas presenting with FFKc. However, in our study, those parameters did not discriminate enough between both groups. Kerautret et al.
37 reports a case of unilateral keratectasia after LASIK with similar values of CH and CRF, but the shape of the infrared and air pressure curves was different in the contralateral eyes. In our study, the shape of the air pressure curve was different between the case and control eyes. At comparable central corneal thickness, corneas of the case group were applanated faster and at lower pressures for inward and outward applanation pressures than corneas of the control group. Moreover, the shape of the infrared curve was different between the case and control eyes and seems to provide qualitative data on the biomechanical properties of corneas. The higher the infrared signal intensity and the tighter the width at half the maximum value, the more the cornea is applanated regularly with a shorter delay. In our study, at inward and outward pressure, FFKc corneas seemed to be applanated less regularly and with a longer delay. There was no significant difference in the full width at half the maximum at outward pressure applanation (fwhm2) between the groups, but the range of the values in the case group was wider than that in the control group. There is probably a less predictable infrared signal reception at outward applanation for case corneas, meaning that such corneas are more flexible and dissipate the infrared beam at the corneal apex. Moreover, the infrared signal is less dependent on CCT in the control group than in the case group, suggesting a quite similar corneal response to air pressure in this group. CCT could be a more important parameter in corneas presenting a latent biomechanical instability; such corneas seemed to be more flexible when narrower than expected for control corneas.
Elasticity refers to how a material deforms in response to an external stress and returns to its original shape along the same stress–strain pathway when the imposed stress is removed. Hysteresis is a viscoelastic property defined as the difference in elastic behavior under loading and unloading stresses, with the material regaining its original shape along a different stress–strain pathway.
The ORA is the first device to allow exploration of the biomechanical properties of the cornea in vivo. CH, supposed to represent its viscoelastic properties, is calculated as the difference of the two pressure values inducing inward and outward applanations. The analysis of the air pressure and infrared curves at inward and outward applanation provides more information on the corneal biomechanics that are not considered at this moment by the ORA software. At inward applanation, peak1, fwhm1, P1, and time P1 are parameters representing the elastic behavior of the cornea under loading; whereas, at outward applanation, peak2, fwhm2, P2, time P2, and DID indicate the elastic behavior of the cornea under unloading. These parameters show the deformation of the cornea, not just its shear strength, represented by hysteresis.
In keratoconic eyes, there is a decrease in the diameter of collagen fibrils associated with an alteration of the regular orthogonal arrangement of the collagen fibril layers above all in the center of the cornea. Moreover, there is a decrease of proteoglycans in the extracellular matrix. Thus, these histologic alterations modify the elastic response of the cornea to an external stress and could precede morphologic deformations.
38–41 The analysis of the corneal elasticity in normal and keratoconic eyes could allow a screening of early biomechanical changes of the cornea.
CH and CRF have to be interpreted according to the CCT, and CRF seems to be the better parameter for screening FFKc. On ROC curves, CH and CRF alone do not allow the screening of such corneas with good sensitivity and specificity; but these curves could be helpful in determining the risk of having a silent biomechanical instability of the cornea according to CH and CRF sensitivities in a CCT group.
Many studies report methods of screening FFKc in the preoperative examination for corneal refractive surgery, but none is totally efficient. The analysis of topographical data remains the most used and the most described method of screening such corneas. Wilson et and Klyce
42 and Rabinowitz
43 described suspect topographical patterns on the mapping of the corneal anterior surface. Irregular astigmatism, asymmetric bowtie, skewed radial axes, or abnormal anterior corneal surface steepening were considered suggestive of FFKc.
42–44 Other studies described a quantitative analysis of the corneal topography. A central keratometry value of more than 47.2 D or a difference of more than 1.4 D between the inferior and the superior average keratometry values of five points at 30° intervals, 3 mm from the center of the cornea were also considered suggestive.
45–47 Finally, the KISA index, associating all the values of this parameter, was produced.
20
Moreover, an elevation of the posterior surface of the cornea by more than 40 μm, analyzed by Orbscan or Pentacam (Oculus, Wetzlar, Germany) suggests FFKc.
48–51 Tanabe et al.
52 described suspect corneas as having greater indices than normal corneas on videokeratography analysis. Moreover, on wavefront analysis, there was a more significant amount of high-order aberrations as third-order comatic aberrations for such corneas.
53,54
All these devices indicate, directly or indirectly, corneal morphology, but none explore its biomechanical properties. Most surgeons recommend for safety a residual stromal bed of more than 250 μm to limit biomechanical weakness after a photoablative procedure.
6,14–16,55–57 The reproducibility of photoablation with an excimer laser and a better predictability of the corneal flap thickness with a femtolaser allow better prediction of the residual stromal bed (RSB) thickness.
58–62 However, analysis of corneal morphology during the preoperative examination and respect to the anatomic guidelines during the photoablative procedure are necessary but not sufficient. Many publications report a keratectasia with a residual stromal bed of more than 250 μm, revealing an FFKc that could affect 49% of eyes.
15,63–66 Some other publications report a corneal stability after photoablation with a shallower RSB.
67–69 There is a difference between each cornea in biomechanical properties and a difference in biomechanical behavior after photoablation. The corneal photoablation changes the intrastromal strength and modifies its viscoelastic properties; keratectasia results in a deformation of the central cornea by a viscoelastic phenomenon.
37,70,71 These results highlight the need to develop a device exploring the corneal biomechanical properties. The development of a corneal biomechanical score to categorize each cornea and an improved predictability of biomechanical weakening induced by a photoablative procedure according to ametropia could optimize the management of patients in refractive surgery.
In our study, the case group had a high risk of keratoconus with no suspect sign on corneal topography. There was a difference in viscoelastic response to air pressure between both groups, although the corneal topography was similar. This study confirms the relevance of the examination of corneal biomechanics. The ORA seems to provide a qualitative analysis of corneas and could be helpful in screening for FFKc in association with the analysis of corneal morphology. The analysis of the air pressure curve and of the infrared signal is probably the next step in the development of the ORA, carrying more information about the biomechanical properties of the cornea. A wide study of both these signals in the whole population and an analysis of its association to CH and CRF is needed. Further studies are necessary to confirm these results and to observe the corneal topography and the ORA parameters over time for both groups.