Whatever the technique of keratoplasty used, it is important to know the biomechanical state of the graft, in addition to evaluating its function and transparency. For this purpose, the devices that allow studying its structural status, such as the Ocular Response Analyzer (ORA, Reichert) are useful, and their results should be interpreted in the context of the other explorations of corneal morphology. Our experience in this field is currently based primarily on penetrating keratoplasty (PK) (Figure 1), although the principles that we will discuss may also be applicable to deep anterior lamellar keratoplasty (DALK) and even other techniques.

BIOMECHANICAL PROPERTIES OF THE GRAFT AND CONTROL OF INTRAOCULAR PRESSURE

Keratoplasty causes a change in the biomechanical characteristics of the cornea in the recipient eye, both by the conditions of the graft and by graft-recipient adaptation and the presence of sutures¹. Until now the modifications and clinical or therapeutic implications that these changes caused were little known.

Glaucoma is one of the most serious complications after PK², which threatens both visual function and graft survival. The topographic, tomographic and pachymetric studies allow knowing the thickness or the regularity of the graft, but not the way of how a high astigmatism, the irregularity of the corneal surface, in the cicatricial interphase or the edema, affect its biomechanical properties and the measurements of intraocular pressure (IOP). To this we must add the difficulties of campimetric control of these patients, especially in the first year of the postoperative period, before the removal of the surgical sutures and the definitive optical correction. The measurement of the biomechanical parameters of the cornea with a technology such as the ORA allows a more accurate assessment of the IOP in these circumstances and in particular on the possible indication of new surgeries (correction of astigmatism, secondary implants, etc.).

Limitations of applanation tonometry in keratoplasty

Goldmann applanation tonometry (GAT) is considered the "gold standard" for measuring IOP. However, since it was described that central corneal thickness can significantly affect their measurements⁴, new techniques have gained importance³. In the case of PK, correction of IOP reading by GAT should not be limited to corneal thickness, since the state of the graft and the magnitude of the astigmatism can also affect it^5,6.

GAT is based on the law of Imbert-Fick, which determines the pressure needed to flatten a perfect dry sphere with thin walls. Goldmann found that a diameter of 3.06 mm is the most suitable for corneal applanation, since the resistance to it in that area is balanced by the capillary attraction of the lacrimal meniscus around the tonometer⁷. This, however, assumes that all corneas are spherical, have the same radius of curvature and have the same rigidity, which in general does not occur after PK.

THE OCULAR RESPONSE ANALYZER

Developed by Reichert (Depew, NY, USA) this device uses a dynamic bidirectional applanation procedure. It generates a measure of IOP that correlates well with the GAT (IOPg). It also produces new parameters: the so-called corneal hysteresis (CH) and the corneal resistance factor (CRF), which represent biomechanical properties of the cornea, as well as a "corneal-compensated IOP" (IOPcc) 8. In addition, the morphology of the ORA signal allows the identification of characteristic patterns of normal or pathological situations⁹.

Corneal hysteresis (CH)

Elastic materials are those that deform proportionally to the force applied, regardless of the time of application. On the contrary, in viscous materials the relationship between the deformation and the applied force depends on the time of action. Viscoelastic materials participate in both behaviors depending on the circumstances and time. The human cornea is a complex structure with viscoelastic biomechanical characteristics. CH is an indicator of the corneal buffering capacity – of absorbing and dissipating mechanical energy –. It is considered that CH is independent of corneal curvature, corneal astigmatism, visual acuity and axial length. Patients with low CH ("soft cornea") are prone to various ocular diseases and complications after refractive surgery¹⁰.

Functioning of the ORA

The ORA acts as a non-contact tonometer using an air jet but, due to its dynamic nature, it records and analyzes the biomechanical properties of the cornea (Figure 2). The two values of pressure in mmHg (P1, P2), obtained in individual moments of flattening, correspond to the IOP according to the Imber-Fick law, but do not coincide with each other. Their average is considered a value equivalent to that of a GAT (IOPg) and their difference, which is due to the viscous properties of the cornea, is used to calculate the corneal hysteresis [CH = P1 - P2].

Corneal-compensated intraocular pressure (IOPcc)

The corneal-compensated IOP is obtained by the formula [IOPcc = P2 - K x P1], where K is a constant of value 0.43. The IOPcc would represent a value of IOP not influenced by the corneal resistance during applanation, that is, independent of corneal properties such as pachymetry or the degree of corneal rigidity. It is more accurate than GAT in patients with keratoconus, Fuchs' dystrophy and normal IOP glaucoma. It also does not depend on the operator and remains constant after LASIK refractive surgery.

Corneal resistance factor (CRF)

The so-called corneal resistance factor is calculated with the formula [CRF = P1 - 0.7 x P2]. It is an indicator that encompasses both the viscosity and the elasticity of the corneal tissues. It correlates with the central corneal thickness (CCT) and the IOPg but not with the IOPcc. While CH represents the ability of the corneal tissues to absorb energy by viscous displacement of the tissue fluid, the CRF encompasses the entire corneal response to that force including the elastic resistance.

Morphology of the signal of the ORA

The precise shape of the flattening signal (of the "peaks") can be considered as the "fingerprint" of the dynamic behavior of the cornea, and the analysis of a series of morphological parameters that define it allows distinguishing between normal and pathological signals.

BIOMECHANICAL PROPERTIES OF CORNEAL GRAFT

In certain pathologies such as keratoconus, corneal dystrophies and some types of glaucoma, as well as after keratoplasty, there is a weakness in the corneal structure that results in decreased biomechanical CH and/or CRF values^9-12. This, together with other morphological aspects, contributes to modify the accuracy of the GAT measurements. In these situations, the ORA offers a more real IOP value (IOPcc).

The measurement of the biomechanical parameters can be of interest to assess how the evolution of the graft affects the corneal structure. We do not know the effects of a tangential circular scar of total thickness and the transcendence of some morphological and structural changes that can suffer. In the case of deep anterior lamellar keratoplasty (DALK) it is possible that biomechanical effects are also generated at the interphase level, depending on their scarring process.

Our experience in penetrating keratoplasty

PK can involve situations of high astigmatism, rejection edema, stromal infiltration, epithelial alterations, surface irregularity, which make it difficult to measure the true IOP. The main contribution of the ORA is the assessment of the biomechanical profile of the cornea and its influence on the estimation of IOP. The IOPcc gives more reliable values and when compared with the IOPg we appreciate their differences with the GAT. The results of a study of the biomechanical profiles of 59 eyes of patients subjected to PK show how the state of the graft affects them and this, in turn, to the determination of IOP, independently of the corneal thickness, radius or corneal curvature¹².

The PK group showed a decrease in CH and CRF and an IOPcc higher than IOPg, compared to a control group of subjects with healthy corneas (Figure 3). In these cases, there is a direct relationship with the status of the graft: those remaining transparent show signs and values similar to normal eyes (Figure 4), while grafts with rejection, failure or edema, have atypical signals, lower CH and values of higher IOPcc, frequently > 21 mmHg.

Regarding the quality of the signals in the cases of PK, these were similar to those of patients without pathology in cases of transparent grafts with good visual acuity, regardless of whether the sutures had been removed or not (Figure 5). In non-transparent grafts or with signs of chronic rejection, we find atypical signs, often a low CH and an IOPcc higher than the IOPg. Sometimes glaucomatous damage was evident in the papillary exploration. In the cases of corneal edema due to endothelial rejection, a high pachymetry is observed with low CH and CRF values; usually, low amplitude repeated signals are obtained, similar to those of advanced keratoconus. They indicate corneal biomechanical deterioration, but the values obtained are not reliable (Figure 6).

Comparison with data in the literature

Although PK is the corneal surgical procedure that involves the most biomechanical changes – and unlike what happens in refractive surgery – there are few studies that study the biomechanical properties of the cornea in eyes subjected to PK. Shin et al.¹³ compared the results in 26 eyes treated with PK with those of the contralateral eye – regardless of the underlying pathology. In the transplanted eyes, they found average values of CH = 8.95 ± 2.59, which are similar to those of our study (CH = 8.54 ± 2.27), but significantly lower than those of the contralateral eye (CH = 9.78 ± 1.45), which are in turn lower than those found in the control group in our study (CH = 10.75 ± 1.55). This may be due to the presence, in this work, of subclinical corneal pathology in the contralateral eyes used as controls.

In the same study, IOPg and IOPcc were significantly higher in the PK group (19.2 ± 7.3 and 20.8 ± 7.8 mmHg, respectively) than in the contralateral eyes (15.0 ± 3.0). and 16.2 ± 2.4 mmHg), differences that were significant in both cases (p = 0.01). In our study, the IOPg after the PK was 16.4 ± 6.6 mmHg (range 4.4-38.5) and the IOPcc was 18.9 ± 7.6 mmHg (range 7.0-50, 7). In both studies we found a mean IOPg inferior to the IOPcc. This reflects the utility of the ORA in the measurement of a more real IOP in transplanted corneas with altered biomechanical properties. The results from Shin et al. coincide with our results in the wide range of IOP values found and in a high standard deviation that reflects the heterogeneity of the samples, with some extreme values of IOP in transplanted corneas. In our study, the mean CCT was 551 ± 80 μm in the transplanted eyes, superior to that obtained by Shin et al., of 489 ± 90 μm.

The eyes with PK in our study show biomechanical values (CH and CRF) significantly lower than in the control eyes, despite having a mean CCT equal or higher. This may be due to the fact that we included cases with corneal edema with CCT > 600 μm, which increases the average CCT and its range in our study. On the other hand, our results are similar to those found by Laiquzzaman et al.¹⁴, with lower CH and CRF values in eyes with PK than in healthy eyes, but CCT of 556 ± 69 μm, without significant differences with the normal population.

Yenerel et al.¹⁵ compared corneal biomechanical properties in patients with keratoconus, PK for keratoconus and normal eyes. In the PK group they obtained mean values of CH and CRF lower than in the control group, but significantly higher than in the non-operated keratoconus. They conclude that PK has a beneficial effect on the biomechanics of the cornea in eyes with keratoconus, which thus approximate their parameters to those of normal eyes.

Evaluation of the signals obtained with the ORA

In cases of PK, ORA signs of atypical morphology and altered biomechanical values are frequent, especially in cases of corneal edema, signs of rejection or glaucoma. On the other hand, we agree with Shin et al. in that cases of transparent PK, with low astigmatism and normal IOPcc, the signals and values are similar to normal eyes. Spörl et al.¹⁶ studied eyes with PK and other corneal pathologies, and also conclude that the altered values of CRF and CH in these cases may reflect structural changes of the cornea.

Our experience shows that the ORA is especially useful for the control of IOP in cases of rejection, in which there is an increase in the CCT and a decrease in CH, and in the evolutionary monitoring of these patients. Non-transparent grafts show repeatedly atypical signals similar to corneas with ectasia and often present IOPcc values higher than the IOPg, which in our series determined the establishment of an antiglaucomatous treatment, after evidencing a campimetric affectation and/or papillary excavation.

BIOMECHANICS IN CORNEAL EDEMA

In PK, there is a certain degree of transient postoperative corneal edema, and in cases of rejection or permanent endothelial failure edema will occur. Frequently, however, old grafts with sparse endothelial population maintain good transparency but with increased thickness. In our study, we observed that edema in a PK is reflected in an increase in CCT, a statistically significant decrease in CH and CRF, similar to that found in endothelial dystrophies with edema¹¹.

The presence of edema in the PK leads to a change in its biomechanical properties, may lead to underestimation of the IOP and cause delays in the diagnosis of glaucoma. The use of more reliable values such as the IOPcc makes it possible to avoid irreversible glaucomatous damage that can cause the graft to fail and overshadow the prognosis of a possible retransplant. We have observed a beneficial effect of the hypotensive treatment also in cases of rejection in which the edema causes an underestimation of the real IOP, which in turn may be aggravated by a response to corticosteroids. In these cases, the reduction in IOP is accompanied by a decrease in the CCT, probably due to a reduction in edema. This coincides with what was observed in patients after cataract surgery explored with ORA¹⁷. They show a significant decrease in the values of CH and CRF in the early postoperative period, due to the transitory edema, which recover after three months.